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1
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Shah KS, Makaryus AN. Navigating Diversity: Optimizing Data Collection for Cardiovascular Health. Am J Med 2024; 137:1027-1029. [PMID: 39097129 DOI: 10.1016/j.amjmed.2024.07.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 07/10/2024] [Accepted: 07/14/2024] [Indexed: 08/05/2024]
Affiliation(s)
- Kevin S Shah
- University of Utah Health Sciences Center, Salt Lake City
| | - Amgad N Makaryus
- Donald and Barbara Zucker School of Medicine at Hofstra/Northwell & Nassau University Medical Center, East Meadow, NY.
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2
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Ibeh C, Tom SE, Marshall RS, Elkind MSV, Willey JZ. Racial-Ethnic disparities in stroke prevalence among patients with heart failure. J Clin Neurosci 2024; 123:173-178. [PMID: 38583373 PMCID: PMC11045301 DOI: 10.1016/j.jocn.2024.03.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 03/06/2024] [Accepted: 03/29/2024] [Indexed: 04/09/2024]
Abstract
Racial-ethnic disparities exist in the prevalence and outcomes of heart failure (HF) and are presumed to be related to differences in cardiovascular risk factor burden and control. There is little data on stroke disparities among patients with HF or the factors responsible. We hypothesized disparities in stroke prevalence exist among patients with HF in a manner not fully explained by burden of cardiovascular disease. We analyzed data from the National Health and Nutrition Examination Survey (1999-2014). Cardiovascular profiles were compared by race/ethnicity. Using survey-weighted models, effect modification of the relationship between HF and stroke by race/ethnicity was examined adjusting for cardiovascular profiles. Of 40,437 participants, 2.5 % had HF. The HF cohort had a greater proportion of White and Black participants (77 % vs 74 % and 15 % vs 12 %, respectively) and fewer participants of Hispanic ethnicity (8 % vs 14 %). Stroke was 8 times more prevalent in HF (19.6 % vs 2.3 %, <0.001). Among individuals with HF, race-ethnic differences were identified in the prevalence and mean values of vascular risk factors but were largely driven by higher rates in Black participants. There was significant interaction between HF and race/ethnicity; HF increased the odds of stroke over 7-fold in participants of Hispanic ethnicity (aOR: 7.84; 95 % CI: 4.11-15.0) but to a lesser extent in Black and White participants (Black aOR: 2.49; 95 % CI: 1.72-3.60; White aOR: 3.36; 95 % CI: 2.57-4.40). People of Hispanic ethnicity with HF have a disproportionately higher risk of stroke in a manner not fully explained by differences in vascular risk profiles.
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Affiliation(s)
- Chinwe Ibeh
- Division of Stroke, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
| | - Sarah E Tom
- Department of Neurology, Division of Neurology Clinical Outcomes Research and Population Science and the Department of Epidemiology, Columbia University Irving Medical Center, New York, NY, USA
| | - Randolph S Marshall
- Division of Stroke, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA
| | - Mitchell S V Elkind
- Department of Neurology, Vagelos College of Physicians and Surgeons and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
| | - Joshua Z Willey
- Division of Stroke, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA
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3
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Octavius GS, Meliani F, Heriyanto RS, Yanto TA. Systematic review of hematidrosis: Time for clinicians to recognize this entity. World J Dermatol 2023; 11:7-29. [DOI: 10.5314/wjd.v11.i2.7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2022] [Revised: 10/12/2022] [Accepted: 11/29/2022] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND Hematidrosis is a sporadic disease, to a point where its existence is still denied up to date. It is also linked to stigmata, psychological roots, and religious beliefs, whih has strengthened clinicians' disbelief in hematidrosis.
AIM To conduct a thorough review to classify the likelihood of hematidrosis cases.
METHODS We searched PubMed, Science Direct, Medline, and Google Scholar, as well as four different preprint databases, including Medrxiv, Research Square, SSRN, and Biorxiv. We included studies from 1996 onwards, with no limitation on language. Hematidrosis was classified as "unlikely", "likely", and "highly likely".
RESULTS There are 74 articles with 106 hematidrosis cases. India (n = 40) and China (n = 11) report the most cases. Patients are mostly female (76.5%) with a median age of 13 years. The head region is the most common bleeding site (n = 168/254). Headaches (26.9%) and abdominal pain (16.4%) are the most common prodromes. Beta-blockers (43%) and anxiolytic (23.2%) are the most commonly prescribed pharmacotherapy. Psychotherapy (37.5%) and counseling (32.5%) are the most utilized non-pharmacotherapy measures. Only 41.1% and 19.8% of all cases reach complete resolution and are highly likely to be hematidrosis, respectively.
CONCLUSION Although hematidrosis is rare and the pathophysiology is still largely unknown, that does not mean hematidrosis does not exist. It is important to note that the most frequent trigger factors are either anxiety, fear, or excessive stress. Clinicians need to exclude other diagnoses and search for stressors to alleviate the bleeding.
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Affiliation(s)
| | - Fellisa Meliani
- Department of Medicine, Universitas Pelita Harapan, Tangerang 15811, Indonesia
| | | | - Theo Audi Yanto
- Department of Medicine, Universitas Pelita Harapan, Tangerang 15811, Indonesia
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4
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Kim HI, Choi EA, Paik EC, Park S, Hwang YI, Lee JH, Seo SK, Cho S, Choi YS, Lee BS, Park J, Lee S, Lee KR, Yun BH. Identification of Single Nucleotide Polymorphisms as Biomarkers for Recurrent Pregnancy Loss in Korean Women. J Korean Med Sci 2022; 37:e336. [PMID: 36631028 PMCID: PMC9705206 DOI: 10.3346/jkms.2022.37.e336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 10/12/2022] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Single nucleotide polymorphisms (SNPs) are reportedly associated with repeated abortion. Thus, genetic analysis based on race is the key to developing accurate diagnostic tests. This study analyzed the genetic polymorphisms of recurrent pregnancy loss (RPL) patients among Korean women compared to the controls. METHODS In 53 women of RPL group and 50 controls, the genetic analysis was performed. The genotype distribution and allele frequency were analyzed statistically for the difference between the two groups. The association between each SNP marker and RPL risk was analyzed. RESULTS The genotypes of LEPR, endothelial nitric oxide synthase (eNOS), KDR, miR-27a, miR-449b, and tumor necrosis factor-alpha (TNF-α) were analyzed using odds ratio (OR) with 95% confidence intervals (CIs). Only the AG genotype of miR-449b (A>G) polymorphism showed significant association with the risk of RPL when compared to the AA genotype (OR, 2.39). The combination of GG/AG+GG/CA+AA genotypes for eNOS/miR-449b/TNF-α was associated with 7.36-fold higher risk of RPL (OR, 7.36). The GG/AG+GG combination for eNOS/miR-449b showed 2.43-fold higher risk for RPL (OR, 2.43). The combination of AG+GG/CA+AA genotypes for miR-449b/TNF-α showed a significant association with the risk of RPL (OR, 7.60). From the haplotype-based analysis, the G-G-A haplotype of eNOS/miR-449b/TNF-α and the G-A haplotype of miR-449b/TNF-α were associated with increased risk of RPL (OR, 19.31; OR, 22.08, respectively). CONCLUSION There is a significant association between the risk of RPL and miR-449b/TNF-α combination, and therefore, genetic analysis for specific combined genotypes can be an important screening method for RPL in Korean women.
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Affiliation(s)
- Hye In Kim
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Eun A Choi
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | | | | | - Yu Im Hwang
- Bundang Cheil Women's Hospital, Seongnam, Korea
| | - Jae Hoon Lee
- Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea
- Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Seok Kyo Seo
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - SiHyun Cho
- Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea
- Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Young Sik Choi
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Byung Seok Lee
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul, Korea
| | - Jimyeong Park
- Seoul Clinical Laboratories Healthcare Co., Ltd., Yongin, Korea
| | - Sanghoo Lee
- Seoul Clinical Laboratories Healthcare Co., Ltd., Yongin, Korea.
| | - Kyoung-Ryul Lee
- Seoul Clinical Laboratories Healthcare Co., Ltd., Yongin, Korea
| | - Bo Hyon Yun
- Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
- Bundang Cheil Women's Hospital, Seongnam, Korea.
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5
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Fitzsimmons L, Dewan M, Dexheimer JW. Diversity in Machine Learning: A Systematic Review of Text-Based Diagnostic Applications. Appl Clin Inform 2022; 13:569-582. [PMID: 35613914 DOI: 10.1055/s-0042-1749119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
Abstract
OBJECTIVE As the storage of clinical data has transitioned into electronic formats, medical informatics has become increasingly relevant in providing diagnostic aid. The purpose of this review is to evaluate machine learning models that use text data for diagnosis and to assess the diversity of the included study populations. METHODS We conducted a systematic literature review on three public databases. Two authors reviewed every abstract for inclusion. Articles were included if they used or developed machine learning algorithms to aid in diagnosis. Articles focusing on imaging informatics were excluded. RESULTS From 2,260 identified papers, we included 78. Of the machine learning models used, neural networks were relied upon most frequently (44.9%). Studies had a median population of 661.5 patients, and diseases and disorders of 10 different body systems were studied. Of the 35.9% (N = 28) of papers that included race data, 57.1% (N = 16) of study populations were majority White, 14.3% were majority Asian, and 7.1% were majority Black. In 75% (N = 21) of papers, White was the largest racial group represented. Of the papers included, 43.6% (N = 34) included the sex ratio of the patient population. DISCUSSION With the power to build robust algorithms supported by massive quantities of clinical data, machine learning is shaping the future of diagnostics. Limitations of the underlying data create potential biases, especially if patient demographics are unknown or not included in the training. CONCLUSION As the movement toward clinical reliance on machine learning accelerates, both recording demographic information and using diverse training sets should be emphasized. Extrapolating algorithms to demographics beyond the original study population leaves large gaps for potential biases.
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Affiliation(s)
- Lane Fitzsimmons
- College of Agriculture and Life Science, Cornell University, Ithaca, New York, United States
| | - Maya Dewan
- Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States.,Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States
| | - Judith W Dexheimer
- Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States.,Division of Emergency Medicine; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States
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6
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Jensen DEA, Leoni V, Klein-Flügge MC, Ebmeier KP, Suri S. Associations of dietary markers with brain volume and connectivity: A systematic review of MRI studies. Ageing Res Rev 2021; 70:101360. [PMID: 33991658 DOI: 10.1016/j.arr.2021.101360] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 04/22/2021] [Accepted: 05/08/2021] [Indexed: 11/20/2022]
Abstract
The high prevalence of unhealthy dietary patterns and related brain disorders, such as dementia, emphasizes the importance of research that examines the effect of dietary factors on brain health. Identifying markers of brain health, such as volume and connectivity, that relate to diet is an important first step towards understanding the lifestyle determinants of healthy brain ageing. We conducted a systematic review of 52 studies (total n = 21,221 healthy participants aged 26-80 years, 55 % female) that assessed with a range of MRI measurements, which brain areas, connections, and cerebrovascular factors were associated with dietary markers. We report associations between regional brain measures and dietary health. Collectively, lower diet quality was related to reduced brain volume and connectivity, especially in white and grey matter of the frontal, temporal and parietal lobe, cingulate, entorhinal cortex and the hippocampus. Associations were also observed in connecting fibre pathways and in particular the default-mode, sensorimotor and attention networks. However, there were also some inconsistencies in research methods and findings. We recommend that future research use more comprehensive and consistent dietary measures, more representative samples, and examine the role of key subcortical regions previously highlighted in relevant animal work.
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Affiliation(s)
- Daria E A Jensen
- Department of Psychiatry, University of Oxford, OX3 7JX, UK; Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging, University of Oxford, OX37JX, UK.
| | - Virginia Leoni
- Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Italy
| | - Miriam C Klein-Flügge
- Department of Experimental Psychology, Wellcome Centre for Integrative Neuroimaging, University of Oxford, Tinsley building, OX1 3SR, UK
| | | | - Sana Suri
- Department of Psychiatry, University of Oxford, OX3 7JX, UK; Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging, University of Oxford, OX37JX, UK
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7
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Nugent BM, Madabushi R, Buch B, Peiris V, Crentsil V, Miller VM, Bull J, R Jenkins M. Heterogeneity in treatment effects across diverse populations. Pharm Stat 2021; 20:929-938. [PMID: 34396690 DOI: 10.1002/pst.2161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Revised: 07/21/2021] [Accepted: 07/21/2021] [Indexed: 11/12/2022]
Abstract
Differences in patient characteristics, including age, sex, and race influence the safety and effectiveness of drugs, biologic products, and medical devices. Here we provide a summary of the topics discussed during the opening panel at the 2018 Johns Hopkins Center for Excellence in Regulatory Science and Innovation symposium on Assessing and Communicating Heterogeneity of Treatment Effects for Patient Subpopulations: Challenges and Opportunities. The goal of this session was to provide a brief overview of FDA-regulated therapeutics, including drugs, biologics and medical devices, and some of the major sources of heterogeneity of treatment effects (HTE) related to patient demographics, such as age, sex and race. The panel discussed the US Food and Drug Administration's role in reviewing and regulating drugs, devices, and biologic products and the challenges associated with ensuring that diverse patient populations benefit from these therapeutics. Ultimately, ensuring diverse demographic inclusion in clinical trials, and designing basic and clinical research studies to account for the intended patient population's age, sex, race, and genetic factors among other characteristics, will lead to better, safer therapies for diverse patient populations.
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Affiliation(s)
- Bridget M Nugent
- Office of Women's Health, U.S. Food and Drug Administration, Silver Spring, Maryland, USA
| | - Rajanikanth Madabushi
- Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA
| | - Barbara Buch
- Center for Biologics Evaluation & Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA
| | - Vasum Peiris
- Center for Devices and Radiological Health, U.S. Food and Drug Administration, Silver Spring, Maryland, USA
| | - Victor Crentsil
- Office of Drug Evaluation III, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA
| | - Virginia M Miller
- Departments of Surgery, and Physiology and Bioengineering, Mayo Clinic, Rochester, Minnesota, USA
| | - Jonca Bull
- Global Product Development, PPDi, Wilmington, North Carolina, USA
| | - Marjorie R Jenkins
- Office of Women's Health, U.S. Food and Drug Administration, Silver Spring, Maryland, USA
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8
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Khan SR, Manialawy Y, Obersterescu A, Cox BJ, Gunderson EP, Wheeler MB. Diminished Sphingolipid Metabolism, a Hallmark of Future Type 2 Diabetes Pathogenesis, Is Linked to Pancreatic β Cell Dysfunction. iScience 2020; 23:101566. [PMID: 33103069 PMCID: PMC7578680 DOI: 10.1016/j.isci.2020.101566] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 07/20/2020] [Accepted: 09/11/2020] [Indexed: 12/12/2022] Open
Abstract
Gestational diabetes mellitus (GDM) is the top risk factor for future type 2 diabetes (T2D) development. Ethnicity profoundly influences who will transition from GDM to T2D, with high risk observed in Hispanic women. To better understand this risk, a nested 1:1 pair-matched, Hispanic-specific, case-control design was applied to a prospective cohort with GDM history. Women who were non-diabetic 6-9 weeks postpartum (baseline) were monitored for the development of T2D. Metabolomics were performed on baseline plasma to identify metabolic pathways associated with T2D risk. Notably, diminished sphingolipid metabolism was highly associated with future T2D. Defects in sphingolipid metabolism were further implicated by integrating metabolomics and genome-wide association data, which identified two significantly enriched T2D-linked genes, CERS2 and CERS4. Follow-up experiments in mice and cells demonstrated that inhibiting sphingolipid metabolism impaired pancreatic β cell function. These data suggest early postpartum alterations in sphingolipid biosynthesis contribute to β cell dysfunction and T2D risk.
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Affiliation(s)
- Saifur R. Khan
- Department of Physiology, University of Toronto, ON, Canada
- Advanced Diagnostics, Metabolism, Toronto General Research Institute, ON, Canada
| | - Yousef Manialawy
- Department of Physiology, University of Toronto, ON, Canada
- Advanced Diagnostics, Metabolism, Toronto General Research Institute, ON, Canada
| | | | - Brian J. Cox
- Department of Physiology, University of Toronto, ON, Canada
- Department of Obstetrics and Gynaecology, University of Toronto, ON, Canada
| | - Erica P. Gunderson
- Kaiser Permanente Northern California, Division of Research, Oakland, CA, USA
| | - Michael B. Wheeler
- Department of Physiology, University of Toronto, ON, Canada
- Advanced Diagnostics, Metabolism, Toronto General Research Institute, ON, Canada
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Abstract
In January 2015, President Barack Obama unveiled the "Precision Medicine Initiative," a nationwide research effort to help bring an effective, preventive, and therapeutic approach to medicine. The purpose of the initiative is to bring a precise understanding of the genetic and environmental determinants of disease into clinical settings across the United States.1 The announcement was coupled with $216 million provided in the President's proposed budget for a million-person national research cohort including public and private partnerships with academic medical centers, researchers, foundations, privacy experts, medical ethicists, and medical product innovators. The Initiative promises to expand the use of precision medicine in cancer research and modernize regulatory approval processes for genome sequencing technologies. In response, Congress passed the 21st Century Cures Act in December 2016, authorizing a total of $1.5 billion over 10 years for the program.2 Although the Precision Medicine Initiative heralds great promise for the future of disease treatment and eradication, its implementation and development must be carefully guided to ensure that the millions of federal dollars expended will be spent equitably. This commentary discusses two key threats to the Precision Medicine Initiative's ability to proceed in a manner consistent with the United States Constitutional requirement that the federal government shall not "deny to any person . . . the equal protection of the laws."3 In short, this commentary sounds two cautionary notes, in order to advance precision medicine equity. First, achieving precision medicine equity will require scientists and clinicians to fulfill their intellectual, moral, and indeed legal duty to work against abusive uses of precision medicine science to advance distorted views of racial group variation. Precision medicine scientists must decisively denounce and distinguish this Initiative from the pseudo-science of eugenics - the immoral and deadly pseudo-science that gave racist and nationalist ideologies what Troy Duster called a "halo of legitimacy" during the first half of the 20th century.4 Second, to combat the social threat to precision medicine, scientists must incorporate a comprehensive, ecological understanding of the fundamental social and environmental determinants of health outcomes in all research. Only then will the Precision Medicine Initiative live up to its potential to improve and indeed transform health care delivery for all patients, regardless of race, color, or national origin.
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Trent M, Dooley DG, Dougé J, Cavanaugh RM, Lacroix AE, Fanburg J, Rahmandar MH, Hornberger LL, Schneider MB, Yen S, Chilton LA, Green AE, Dilley KJ, Gutierrez JR, Duffee JH, Keane VA, Krugman SD, McKelvey CD, Linton JM, Nelson JL, Mattson G, Breuner CC, Alderman EM, Grubb LK, Lee J, Powers ME, Rahmandar MH, Upadhya KK, Wallace SB, SECTION ON ADOLESCENT HEALTH, COUNCIL ON COMMUNITY PEDIATRICS, COMMITTEE ON ADOLESCENCE. The Impact of Racism on Child and Adolescent Health. Pediatrics 2019; 144:peds.2019-1765. [PMID: 31358665 DOI: 10.1542/peds.2019-1765] [Citation(s) in RCA: 583] [Impact Index Per Article: 97.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
The American Academy of Pediatrics is committed to addressing the factors that affect child and adolescent health with a focus on issues that may leave some children more vulnerable than others. Racism is a social determinant of health that has a profound impact on the health status of children, adolescents, emerging adults, and their families. Although progress has been made toward racial equality and equity, the evidence to support the continued negative impact of racism on health and well-being through implicit and explicit biases, institutional structures, and interpersonal relationships is clear. The objective of this policy statement is to provide an evidence-based document focused on the role of racism in child and adolescent development and health outcomes. By acknowledging the role of racism in child and adolescent health, pediatricians and other pediatric health professionals will be able to proactively engage in strategies to optimize clinical care, workforce development, professional education, systems engagement, and research in a manner designed to reduce the health effects of structural, personally mediated, and internalized racism and improve the health and well-being of all children, adolescents, emerging adults, and their families.
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Affiliation(s)
- Maria Trent
- Division of Adolescent and Young Adult Medicine, Department of Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, Maryland
| | - Danielle G. Dooley
- Division of General Pediatrics and Community Health and Child Health Advocacy Institute, Children’s National Health System, Washington, District of Columbia; and
| | - Jacqueline Dougé
- Medical Director, Howard County Health Department, Columbia, Maryland
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11
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Nelson SC, Yu JH, Wagner JK, Harrell TM, Royal CD, Bamshad MJ. A content analysis of the views of genetics professionals on race, ancestry, and genetics. AJOB Empir Bioeth 2019; 9:222-234. [PMID: 30608210 DOI: 10.1080/23294515.2018.1544177] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Over the past decade, the proliferation of genetic studies on human health and disease has reinvigorated debates about the appropriate role of race and ancestry in research and clinical care. Here we report on the responses of genetics professionals to a survey about their views on race, genetics, and ancestry across the domains of science, medicine, and society. Through a qualitative content analysis of free-text comments from 515 survey respondents, we identified key themes pertaining to multiple meanings of race, the use of race as a proxy for genetic ancestry, and the relevance of race and ancestry to health. Our findings suggest that for many genetics professionals the questions of what race is and what race means remain both professionally and personally contentious. Looking ahead as genomics is translated into the practice of precision medicine and as learning health care systems offer continued improvements in care through integrated research, we argue for nuanced considerations of both race and genetic ancestry across research and care settings.
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Affiliation(s)
- Sarah C Nelson
- a Institute for Public Health Genetics , University of Washington
| | - Joon-Ho Yu
- b Department of Pediatrics , University of Washington
| | - Jennifer K Wagner
- c Center for Translational Bioethics & Health Care Policy , Geisinger Health System
| | | | - Charmaine D Royal
- d Department of African & African American Studies , Duke University
| | - Michael J Bamshad
- b Department of Pediatrics , University of Washington.,e Department of Genome Sciences , University of Washington
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Dallo FJ, Ajrouch KJ, Al-Snih S. The Ancestry Question and Ethnic Heterogeneity: The Case of Arab Americans. INTERNATIONAL MIGRATION REVIEW 2018. [DOI: 10.1111/j.1747-7379.2008.00133.x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
This article uses US Census data to investigate change over time in Arab American profiles. In 2000, a higher proportion of children (0 to 13 years of age), women, and those who lived in the Northeast identified with an Arab/non-Arab ancestry compared to an Arab-only ancestry. In 1980 and 2000, a higher proportion (~90%) of those who identified with an Arab/non-Arab ancestry was US born compared to only one-half of those who identified with an Arab-only ancestry. Those who identified with an Arab-only ancestry were more likely to not be US citizens than those who identified with an Arab/non-Arab ancestry. These findings suggest Arab Americans are a heterogeneous group.
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Affiliation(s)
| | - Kristine J. Ajrouch
- Department of Sociology, Anthropology, Criminology, Eastern Michigan University
| | - Soham Al-Snih
- Rehabilitation Sciences Division/School of Allied Health Sciences, University of Texas Medical Branch
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Towards a more representative morphology: clinical and ethical considerations for including diverse populations in diagnostic genetic atlases. Genet Med 2016; 18:1069-1074. [PMID: 26963283 DOI: 10.1038/gim.2016.7] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2015] [Accepted: 01/06/2016] [Indexed: 02/04/2023] Open
Abstract
An important gap exists in textbooks (or atlases) of dysmorphology used by health-care professionals to help diagnose genetic syndromes. The lack of varied phenotypic images in available atlases limits the utility of these atlases as diagnostic tools in globally diverse populations, causing geneticists difficulty in diagnosing conditions in individuals of different ancestral backgrounds who may present with variable morphological features. Proposals to address the underinclusion of images from diverse populations in existing atlases can take advantage of the Internet and digital photography to create new resources that take into account the broad global diversity of populations affected by genetic disease. Creating atlases that are more representative of the global population will expand resources available to care for diverse patients with these conditions, many of whom have been historically underserved by the medical system. However, such projects also raise ethical questions that are grounded in the complex intersection of imagery, medicine, history, and race and ethnicity. We consider here the benefits of producing such a resource while also considering ethical and practical concerns, and we offer recommendations for the ethical creation, structure, equitable use, and maintenance of a diverse morphological atlas for clinical diagnosis.Genet Med 18 11, 1069-1074.
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14
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National intelligence and private health expenditure: Do high IQ societies spend more on health insurance? INTELLIGENCE 2015. [DOI: 10.1016/j.intell.2015.06.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Conti G, Heckman JJ. Understanding the Early Origins of the Education-Health Gradient: A Framework That Can Also Be Applied to Analyze Gene-Environment Interactions. PERSPECTIVES ON PSYCHOLOGICAL SCIENCE 2015; 5:585-605. [PMID: 21738556 DOI: 10.1177/1745691610383502] [Citation(s) in RCA: 97] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
In this article, we develop a framework for analyzing the causal effects of interventions in the presence of latent factors that could affect outcomes, even in the absence of interventions. This framework will be useful in situations in which genes are included among the latent factors. We estimate the model and study the early origins of observed later-life disparities by education. We determine the role played by cognitive, noncognitive, and early health endowments. We identify the causal effect of education on health and health-related behaviors. We show that family background characteristics and cognitive, noncognitive, and health endowments developed by age 10 are important determinants of health disparities at age 30. We also show that not properly accounting for personality traits results in overestimation of the importance of cognitive ability in determining later health. Selection on preexisting traits explains more than half of the observed differences in poor health and obesity. Education has an important causal effect in explaining differences in smoking rates. There are significant gender differences. We go beyond the current literature, which typically estimates mean effects, to compute distributions of treatment effects. We show that the effect of education on health varies among individuals who are similar in their observed characteristics, and how a mean effect can hide gains and losses for different individuals. This analysis highlights the crucial role played by promotion of good health at an early age and the importance of prevention in the reduction of health disparities. We speculate about how the model can be applied to genetic studies.
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Affiliation(s)
| | - James J Heckman
- Department of Economics, University of Chicago, IL School of Economics, University College Dublin, Ireland
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16
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Abstract
An extensive literature documents the existence of pervasive and persistent child health, development, and health care disparities by race, ethnicity, and socioeconomic status (SES). Disparities experienced during childhood can result in a wide variety of health and health care outcomes, including adult morbidity and mortality, indicating that it is crucial to examine the influence of disparities across the life course. Studies often collect data on the race, ethnicity, and SES of research participants to be used as covariates or explanatory factors. In the past, these variables have often been assumed to exert their effects through individual or genetically determined biologic mechanisms. However, it is now widely accepted that these variables have important social dimensions that influence health. SES, a multidimensional construct, interacts with and confounds analyses of race and ethnicity. Because SES, race, and ethnicity are often difficult to measure accurately, leading to the potential for misattribution of causality, thoughtful consideration should be given to appropriate measurement, analysis, and interpretation of such factors. Scientists who study child and adolescent health and development should understand the multiple measures used to assess race, ethnicity, and SES, including their validity and shortcomings and potential confounding of race and ethnicity with SES. The American Academy of Pediatrics (AAP) recommends that research on eliminating health and health care disparities related to race, ethnicity, and SES be a priority. Data on race, ethnicity, and SES should be collected in research on child health to improve their definitions and increase understanding of how these factors and their complex interrelationships affect child health. Furthermore, the AAP believes that researchers should consider both biological and social mechanisms of action of race, ethnicity, and SES as they relate to the aims and hypothesis of the specific area of investigation. It is important to measure these variables, but it is not sufficient to use these variables alone as explanatory for differences in disease, morbidity, and outcomes without attention to the social and biologic influences they have on health throughout the life course. The AAP recommends more research, both in the United States and internationally, on measures of race, ethnicity, and SES and how these complex constructs affect health care and health outcomes throughout the life course.
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Physicians' knowledge, beliefs, and use of race and human genetic variation: new measures and insights. BMC Health Serv Res 2014; 14:456. [PMID: 25277068 PMCID: PMC4283084 DOI: 10.1186/1472-6963-14-456] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2014] [Accepted: 09/18/2014] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Understanding physician perspectives on the intersection of race and genomics in clinical decision making is critical as personalized medicine and genomics become more integrated in health care services. There is a paucity of literature in the United States of America (USA) and globally regarding how health care providers understand and use information about race, ethnicity and genetic variation in their clinical decision making. This paper describes the development of three scales related to addressing this gap in the literature: the Bonham and Sellers Genetic Variation Knowledge Assessment Index--GKAI, Health Professionals Beliefs about Race-HPBR, and Racial Attributes in Clinical Evaluation-RACE scales. METHODS A cross-sectional, web survey of a national random sample of general internists in the USA (N = 787) was conducted. Confirmatory factor analysis was used to assess the construct validity of the scales. Scale items were developed through focus groups, cognitive interviews, expert advisory panels, and exploratory factor analysis of pilot data. RESULTS GKAI was measured as a count of correct answers (Mean = 3.28 SD = 1.17). HPBR yielded two domains: beliefs about race as a biological phenomenon (HPBR-BD, alpha = .69, 4 items) and beliefs about the clinical value of race and genetic variation for understanding risk for disease (HPBR-CD alpha = .61, 3 items). RACE yielded one factor (alpha = .86, 7 items). CONCLUSIONS GKAI is a timely knowledge scale that can be used to assess health professional knowledge of race and human genetic variation. HPBR is a promising new tool for assessing health professionals' beliefs about the role of race and its relationship with human genetic variation in clinical practice. RACE offers a valid and reliable tool for assessing explicit use of racial attributes in clinical decision making.
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Perceptions of genetic testing and genomic medicine among drug users. THE INTERNATIONAL JOURNAL OF DRUG POLICY 2014; 26:100-6. [PMID: 25037119 DOI: 10.1016/j.drugpo.2014.06.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2014] [Revised: 06/13/2014] [Accepted: 06/17/2014] [Indexed: 12/20/2022]
Abstract
BACKGROUND Genetic testing will soon enter care for human immunodeficiency virus (HIV) and hepatitis C virus (HCV), and for addiction. There is a paucity of data on how to disseminate genetic testing into healthcare for marginalized populations. We explored drug users' perceptions of genetic testing. METHODS Six focus groups were conducted with 34 drug users recruited from syringe exchange programmes and an HIV clinic between May and June 2012. Individual interviews were conducted with participants reporting previous genetic testing. RESULTS All participants expressed acceptance of genetic testing to improve care, but most had concerns regarding confidentiality and implications for law enforcement. Most expressed more comfort with genetic testing based on individual considerations rather than testing based on race/ethnicity. Participants expressed comfort with genetic testing in medical care rather than drug treatment settings and when specifically asked permission, with peer support, and given a clear rationale. CONCLUSION Although participants understood the potential value of genetic testing, concerns regarding breaches in confidentiality and discrimination may reduce testing willingness. Safeguards against these risks, peer support, and testing in medical settings based on individual factors and with clear rationales provided may be critical in efforts to promote acceptance of genetic testing among drug users.
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Marrie RA, Gryba C. The incidence and prevalence of neuromyelitis optica: a systematic review. Int J MS Care 2014; 15:113-8. [PMID: 24453773 DOI: 10.7224/1537-2073.2012-048] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Interest in neuromyelitis optica (NMO) has increased substantially over the last few years, but it is not known whether NMO has the same geographic and temporal variations in disease risk as multiple sclerosis (MS). We aimed to evaluate the worldwide incidence and prevalence of NMO through a systematic review of published peer-reviewed studies. We performed a search of the English-language literature using MEDLINE and EMBASE from January 1985 to March 2012. Search terms included "neuromyelitis optica," "Devic's," "opticospinal," "incidence," "prevalence," and "epidemiology." We assessed study quality using a standardized instrument. A total of five studies met the inclusion criteria. Three of the studies were from North America, and all studies were published between 2005 and 2012. All studies were of good quality, but only one study reported standardized rates, and subgroup-specific estimates were rarely reported. The incidence of NMO per 100,000 population ranged from 0.053 to 0.40, while the prevalence per 100,000 population ranged from 0.52 to 4.4. Heterogeneity was high among the incidence (I(2) = 68.0%) and prevalence studies (I(2) = 94.0%). This review highlights the limited knowledge regarding the epidemiology of NMO and the importance of obtaining estimates standardized to common populations to enhance comparability of studies from different jurisdictions. Future studies would also benefit from reporting age-, sex-, and race- or ethnicity-specific estimates.
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Affiliation(s)
- Ruth Ann Marrie
- Department of Internal Medicine (RAM, CG) and the Department of Community Health Sciences (RAM), University of Manitoba, Winnipeg, Manitoba, Canada
| | - Caroline Gryba
- Department of Internal Medicine (RAM, CG) and the Department of Community Health Sciences (RAM), University of Manitoba, Winnipeg, Manitoba, Canada
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20
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Owen CM, Goldstein EH, Clayton JA, Segars JH. Racial and ethnic health disparities in reproductive medicine: an evidence-based overview. Semin Reprod Med 2013; 31:317-24. [PMID: 23934691 DOI: 10.1055/s-0033-1348889] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Racial and ethnic health disparities in reproductive medicine exist across the life span and are costly and burdensome to our healthcare system. Reduction and ultimate elimination of health disparities is a priority of the National Institutes of Health who requires reporting of race and ethnicity for all clinical research it supports. Given the increasing rates of admixture in our population, the definition and subsequent genetic significance of self-reported race and ethnicity used in health disparity research is not straightforward. Some groups have advocated using self-reported ancestry or carefully selected single-nucleotide polymorphisms, also known as ancestry informative markers, to sort individuals into populations. Despite the limitations in our current definitions of race and ethnicity in research, there are several clear examples of health inequalities in reproductive medicine extending from puberty and infertility to obstetric outcomes. We acknowledge that socioeconomic status, education, insurance status, and overall access to care likely contribute to the differences, but these factors do not fully explain the disparities. Epigenetics may provide the biologic link between these environmental factors and the transgenerational disparities that are observed. We propose an integrated view of health disparities across the life span and generations focusing on the metabolic aspects of fetal programming and the effects of environmental exposures. Interventions aimed at improving nutrition and minimizing adverse environmental exposures may act synergistically to reverse the effects of these epigenetic marks and improve the outcome of our future generations.
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Affiliation(s)
- Carter M Owen
- Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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21
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The Minnesota Center for Twin and Family Research genome-wide association study. Twin Res Hum Genet 2013; 15:767-74. [PMID: 23363460 DOI: 10.1017/thg.2012.62] [Citation(s) in RCA: 63] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
As part of the Genes, Environment and Development Initiative, the Minnesota Center for Twin and Family Research (MCTFR) undertook a genome-wide association study, which we describe here. A total of 8,405 research participants, clustered in four-member families, have been successfully genotyped on 527,829 single nucleotide polymorphism (SNP) markers using lllumina's Human660W-Ouad array. Quality control screening of samples and markers as well as SNP imputation procedures are described. We also describe methods for ancestry control and how the familial clustering of the MCTFR sample can be accounted for in the analysis using a Rapid Feasible Generalized Least Squares algorithm. The rich longitudinal MCTFR assessments provide numerous opportunities for collaboration.
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22
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Srinivas TR, Poggio ED. Do living kidney donors have CKD? Adv Chronic Kidney Dis 2012; 19:229-36. [PMID: 22732042 DOI: 10.1053/j.ackd.2012.05.008] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2012] [Revised: 05/17/2012] [Accepted: 05/18/2012] [Indexed: 12/18/2022]
Abstract
Living kidney donor transplantation is an increasingly used treatment for end-stage renal disease because it both confers excellent outcomes to transplant recipients, and is considered a safe procedure for prospective donors. The short- and long-term safety of prospective donors is paramount to the continued success of living donation. Although the initial experience with living kidney donors mostly included the healthiest donors, increasing need for organs and secular trends in the general population have subtly reshaped prevailing suitability criteria for donation. As the practice of living donation evolved over time, our understanding of kidney disease has also changed as we embraced the framework of the K-DOQI guidelines. It is not uncommon for donors to fit into some of the K-DOQI guidelines paradigms of risk and disease; however, whether there is a true biological consequence or whether it is a merely semantic conundrum remains unclear. Regardless, this is an important issue, and therefore future efforts should aim at addressing this matter.
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Abstract
The existence of pronounced differences in health outcomes between US populations is a problem of moral significance and public health urgency. Pursuing research on genetic contributors to such disparities, despite striking data on the fundamental role of social factors, has been controversial. Still, advances in genomic science are providing an understanding of disease biology at a level of precision not previously possible. The potential for genomic strategies to help in addressing population-level disparities therefore needs to be carefully evaluated. Using 3 examples from current research, we argue that the best way to maximize the benefits of population-based genomic investigations, and mitigate potential harms, is to direct research away from the identification of genetic causes of disparities and instead focus on applying genomic methodologies to the development of clinical and public health tools with the potential to ameliorate healthcare inequities, direct population-level health interventions or inform public policy. Such a transformation will require close collaboration between transdisciplinary teams and community members as well as a reorientation of current research objectives to better align genomic discovery efforts with public health priorities and well-recognized barriers to fair health care delivery.
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Affiliation(s)
- S M Fullerton
- Department of Bioethics and Humanities, and Center for Genomics and Healthcare Equality, University of Washington, Seattle, WA 98195, USA.
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24
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Lutsey PL, Wassel CL, Cushman M, Sale MM, Divers J, Folsom AR. Genetic admixture is associated with plasma hemostatic factor levels in self-identified African Americans and Hispanics: the Multi-Ethnic Study of Atherosclerosis. J Thromb Haemost 2012; 10:543-9. [PMID: 22332961 PMCID: PMC3361899 DOI: 10.1111/j.1538-7836.2012.04663.x] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
BACKGROUND Epidemiologic studies report that self-identified African Americans typically have higher hemostatic factor levels than do self-identified Caucasians or Hispanics. OBJECTIVE To enhance understanding of phenotypic variation in hemostatic factor levels by race/ethnicity, we evaluated the relationship between genetic ancestry and hemostatic factor levels among Multi-Ethnic Study of Atherosclerosis (MESA) study participants. PATIENTS/METHODS Our sample included 712 African American and 701 Hispanic men and women aged 45 to 84 years. Individual global ancestry was estimated from 199 genetic markers using STRUCTURE. Linear regression models were used to evaluate the relationship between ancestry and hemostatic factor levels, adjusting for age, gender, education, income and study site. RESULTS Among African Americans, mean ± standard deviation (SD) ancestry was estimated as 79.9% ± 15.9% African and 20.1% ± 15.9% European. Each SD (16%) greater African ancestry was associated with 2.1% higher fibrinogen levels (P = 0.007) and 3.5% higher plasmin-antiplasmin (PAP) levels (P = 0.02). Ancestry among African Americans was not related to levels of factor (F)VIII or D-dimer. Mean ± SD estimated ancestry among Hispanics was 48.3% ± 23.8% Native American, 38.8% ± 21.9% European, and 13.0% ± 8.9% African. In Hispanics, each SD (19%) greater African ancestry was associated with 2.7% higher fibrinogen levels (P = 0.009) and 7.9% higher FVIII levels (P = 0.0002). In Hispanics, there was no relation between African ancestry and D-dimer or PAP levels, or between European ancestry and hemostatic factor levels. CONCLUSIONS Greater African ancestry among African Americans and Hispanics was associated with higher levels of several hemostatic factors, notably fibrinogen. These results suggest that genetic heterogeneity contributes, albeit modestly, to racial/ethnic differences in hemostatic factor levels.
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Affiliation(s)
- P L Lutsey
- Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, MN 55454, USA.
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25
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Ned RM, Yesupriya A, Imperatore G, Smelser DT, Moonesinghe R, Chang MH, Dowling NF. The ACE I/D polymorphism in US adults: limited evidence of association with hypertension-related traits and sex-specific effects by race/ethnicity. Am J Hypertens 2012; 25:209-15. [PMID: 21993364 DOI: 10.1038/ajh.2011.182] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND The insertion/deletion (I/D) variant (rs4646994) of the angiotensin I-converting enzyme (ACE) gene is one of the most studied polymorphisms in relation to blood pressure and essential hypertension in humans. The evidence to date, however, on an association of this variant with blood pressure-related outcomes has been inconclusive. METHODS We examined 5,561 participants of the Third National Health and Nutrition Examination Survey (NHANES III), a population-based and nationally representative survey of the United States, who were ≥20 years of age and who self-identified as non-Hispanic white, non-Hispanic black, or Mexican American. Within each race/ethnicity, we assessed genetic associations of the I/D variant with systolic blood pressure (SBP), diastolic blood pressure (DBP), and hypertension, as well as genotype-sex interactions, in four genetic models (additive, dominant, recessive, and codominant). RESULTS The frequency of the I/D variant differed significantly by race/ethnicity (P = 0.001). Among non-Hispanic blacks, the D allele was significantly associated (P < 0.05) with increased SBP in additive and dominant covariate-adjusted models and was also associated with increased DBP in dominant models when participants taking ACE inhibitors were excluded from the analyses. No other significant associations were observed in any race/ethnic group. Significant genotype-sex interactions were detected among Mexican Americans, for whom positive associations with SBP and hypertension were seen among females, but not males. CONCLUSIONS This study gives limited support for association of the ACE I/D variant with blood pressure and for sex-specific effects among particular race/ethnic groups, though we cannot rule out the role of genetic or environmental interactions.
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Affiliation(s)
- Renée M Ned
- Office of Public Health Genomics, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
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26
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Parker LS, Satkoske VB. Ethical dimensions of disparities in depression research and treatment in the pharmacogenomic era. THE JOURNAL OF LAW, MEDICINE & ETHICS : A JOURNAL OF THE AMERICAN SOCIETY OF LAW, MEDICINE & ETHICS 2012; 40:886-903. [PMID: 23289692 DOI: 10.1111/j.1748-720x.2012.00718.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
Disparities in access to, and utilization of, treatment for depression among African-American and Caucasian elderly adults have been well-documented. Less fully explored are the multidimensional factors responsible for these disparities. The intersection of cultural constructs, socioeconomic factors, multiple levels of racism, and stigma attending both mental health issues and older age may help to explain disparities in the treatment of the depressed elderly. Personalized medicine with its promise of developing interventions tailored to an individual's health needs and genetically related response to treatment might seem a promising antidote to the documented underutilization of standard depression treatments by African Americans. However, this paper examines the multidimensional factors associated with disparities in effective treatment of depression among African-American and Caucasian elderly adults and argues the scientific and ethical importance of pursuing various paths to address multiple levels and sources of stigma and mistrust if pharmacogenomics is to help, rather than exacerbate, disparities in depression treatment. Seven recommendations are offered to increase the likelihood that developments in pharmacogenomics will reduce disparities in depression treatment.
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Affiliation(s)
- Lisa S Parker
- Center for Bioethics and Health Law, University of Pittsburgh, USA
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27
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Bliss C. Racial taxonomy in genomics. Soc Sci Med 2011; 73:1019-27. [DOI: 10.1016/j.socscimed.2011.07.003] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2010] [Revised: 07/01/2011] [Accepted: 07/01/2011] [Indexed: 01/17/2023]
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Abstract
Peter Chow-White and Troy Duster examine the question of whether the "digital divide" in health and forensic DNA databases is contributing to racial disparities.
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Affiliation(s)
- Peter A. Chow-White
- School of Communication, Simon Fraser University, Vancouver, British Columbia, Canada
- * E-mail:
| | - Troy Duster
- Department of Sociology, New York University, New York, New York, United States of America
- Department of Sociology, University of California, Berkeley, California, United States of America
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Abstract
As with susceptibility to disease, it is likely that multiple factors interact to influence the phenotype of multiple sclerosis and long-term disease outcomes. Such factors may include genetic factors, socioeconomic status, comorbid diseases, and health behaviors, as well as environmental exposures. An improved understanding of the influence of these factors on disease course may reap several benefits, such as improved prognostication, allowing us to tailor disease management with respect to intensity of disease-modifying therapies and changes in specific health behaviors, in the broad context of coexisting health issues. Such information can facilitate appropriately adjusted comparisons within and between populations. Elucidation of these factors will require careful study of well-characterized populations in which the roles of multiple factors are considered simultaneously.
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Affiliation(s)
- Ruth Ann Marrie
- University of Manitoba, Health Sciences Center, GF-533, 820 Sherbrook Street, Winnipeg, Manitoba, R3A 1R9, Canada.
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31
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Mitchell C, Gregersen N, Krause A. Novel CYP2C9 and VKORC1 gene variants associated with warfarin dosage variability in the South African black population. Pharmacogenomics 2011; 12:953-63. [PMID: 21635147 DOI: 10.2217/pgs.11.36] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
AIM Warfarin is a widely used therapeutic agent for long-term oral anticoagulation worldwide. Its administration is challenging owing to its narrow therapeutic range and serious adverse effects. Several environmental factors and numerous genes, of which CYP2C9 and VKORC1 are the most important, have been associated with interindividual dosage variability. Many studies have been conducted to understand warfarin dosage variability better, the majority of which have been focused on the Caucasian and African-American populations. Very little information is available regarding genetic influences of warfarin dosage variability in the South African black population. MATERIALS & METHODS In this study, we genotyped 213 South African black individuals for CYP2C9 and VKORC1 variants and a small subset of environmental factors that may be responsible for warfarin dosage variability. RESULTS We observed 26 novel SNPs and seven previously described CYP2C9 variants and three previously described but no novel VKORC1 SNPs. Only 11 of the CYP2C9 variants and two of the VKORC1 variants were observed at high enough allele frequencies to assess their impact on warfarin dosage. CONCLUSION We demonstrate that CYP2C9*8 and two novel CYP2C9 SNPs (g.16179 and g.46028) are associated with a decrease in warfarin dosage, β-blockers are independently associated with a decrease in warfarin dosage and two known VKORC1 variants (rs7200749 and rs7294) are associated with an increase in warfarin dosage. The CYP2C9 and VKORC1 variants and a small subset of environmental factors used in the study explain approximately 45% of warfarin dosage variability in the South African black population.
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Affiliation(s)
- Cathrine Mitchell
- Division of Human Genetics, The National Health Laboratory Service & School of Pathology, The University of Witwatersrand, Johannesburg, South Africa
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The impact of race/ethnicity on baseline characteristics and the burden of coronary atherosclerosis in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial. Am Heart J 2011; 161:755-63. [PMID: 21473976 DOI: 10.1016/j.ahj.2010.12.013] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2009] [Accepted: 12/10/2010] [Indexed: 11/21/2022]
Abstract
OBJECTIVES We aimed to test the impact of race/ethnicity on coronary artery disease (CAD) after adjusting for baseline risk factors. BACKGROUND Whether race/ethnicity remains an important determinant of the burden of CAD even among patients with long-standing type 2 diabetes (diabetes mellitus) and established CAD is unknown. METHODS Analysis of baseline data from the BARI 2D trial (January 1, 2001, to March 31, 2005) was performed. Myocardial jeopardy index (MJI) was evaluated by a blinded core angiographic laboratory. Multivariate regression analysis was performed to determine the independent association of race/ethnicity on the burden of CAD after adjusting for baseline risk factors. Data were collected from US and Canadian academic and community hospitals. The baseline analysis was performed on patients with long-standing diabetes and documented CAD with no prior revascularization at study entry (n = 1,331). The main outcome measure was MJI, which represents the percentage of myocardium jeopardized by significant lesions (≥50%). The secondary outcome measure was ≥2 lesions with ≥50% stenosis. RESULTS Risk factors varied significantly among racial/ethnic groups. Blacks were significantly more likely to be women, have no health insurance, be current smokers, have higher body mass index, have hypertension, have a longer duration of diabetes, a higher hemoglobin A(1c) level, and were more likely to be taking insulin. Their mean total, low-density lipid, and high-density lipid cholesterol levels were higher, whereas their triglycerides were lower than others. After controlling for baseline risk factors, blacks had a significantly lower burden of CAD; the adjusted MJI was 5.43 U lower (95% CI -9.13 to -1.72), and the adjusted number of lesions was 0.53 fewer (95% CI -0.88 to -0.18) in blacks compared to whites. CONCLUSIONS In the BARI 2D trial, self-reported race/ethnicity is associated with important differences in baseline risk factors and is a powerful predictor of the burden of CAD adjusting for such baseline differences. These findings may help direct medical intervention and resources and further investigation into the basis of racial/ethnic differences in CAD burden.
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Dumitrescu L, Glenn K, Brown-Gentry K, Shephard C, Wong M, Rieder MJ, Smith JD, Nickerson DA, Crawford DC. Variation in LPA is associated with Lp(a) levels in three populations from the Third National Health and Nutrition Examination Survey. PLoS One 2011; 6:e16604. [PMID: 21305047 PMCID: PMC3030597 DOI: 10.1371/journal.pone.0016604] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2010] [Accepted: 12/22/2010] [Indexed: 02/06/2023] Open
Abstract
The distribution of lipoprotein(a) [Lp(a)] levels can differ dramatically across diverse racial/ethnic populations. The extent to which genetic variation in LPA can explain these differences is not fully understood. To explore this, 19 LPA tagSNPs were genotyped in 7,159 participants from the Third National Health and Nutrition Examination Survey (NHANES III). NHANES III is a diverse population-based survey with DNA samples linked to hundreds of quantitative traits, including serum Lp(a). Tests of association between LPA variants and transformed Lp(a) levels were performed across the three different NHANES subpopulations (non-Hispanic whites, non-Hispanic blacks, and Mexican Americans). At a significance threshold of p<0.0001, 15 of the 19 SNPs tested were strongly associated with Lp(a) levels in at least one subpopulation, six in at least two subpopulations, and none in all three subpopulations. In non-Hispanic whites, three variants were associated with Lp(a) levels, including previously known rs6919246 (p = 1.18 × 10(-30)). Additionally, 12 and 6 variants had significant associations in non-Hispanic blacks and Mexican Americans, respectively. The additive effects of these associated alleles explained up to 11% of the variance observed for Lp(a) levels in the different racial/ethnic populations. The findings reported here replicate previous candidate gene and genome-wide association studies for Lp(a) levels in European-descent populations and extend these findings to other populations. While we demonstrate that LPA is an important contributor to Lp(a) levels regardless of race/ethnicity, the lack of generalization of associations across all subpopulations suggests that specific LPA variants may be contributing to the observed Lp(a) between-population variance.
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Affiliation(s)
- Logan Dumitrescu
- Center for Human Genetics Research, Vanderbilt University, Nashville, Tennessee, United States of America
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, United States of America
| | - Kimberly Glenn
- Center for Human Genetics Research, Vanderbilt University, Nashville, Tennessee, United States of America
| | - Kristin Brown-Gentry
- Center for Human Genetics Research, Vanderbilt University, Nashville, Tennessee, United States of America
| | - Cynthia Shephard
- Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America
| | - Michelle Wong
- Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America
| | - Mark J. Rieder
- Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America
| | - Joshua D. Smith
- Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America
| | - Deborah A. Nickerson
- Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America
| | - Dana C. Crawford
- Center for Human Genetics Research, Vanderbilt University, Nashville, Tennessee, United States of America
- Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee, United States of America
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Marigorta UM, Lao O, Casals F, Calafell F, Morcillo-Suárez C, Faria R, Bosch E, Serra F, Bertranpetit J, Dopazo H, Navarro A. Recent human evolution has shaped geographical differences in susceptibility to disease. BMC Genomics 2011; 12:55. [PMID: 21261943 PMCID: PMC3039608 DOI: 10.1186/1471-2164-12-55] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2010] [Accepted: 01/24/2011] [Indexed: 01/01/2023] Open
Abstract
Background Searching for associations between genetic variants and complex diseases has been a very active area of research for over two decades. More than 51,000 potential associations have been studied and published, a figure that keeps increasing, especially with the recent explosion of array-based Genome-Wide Association Studies. Even if the number of true associations described so far is high, many of the putative risk variants detected so far have failed to be consistently replicated and are widely considered false positives. Here, we focus on the world-wide patterns of replicability of published association studies. Results We report three main findings. First, contrary to previous results, genes associated to complex diseases present lower degrees of genetic differentiation among human populations than average genome-wide levels. Second, also contrary to previous results, the differences in replicability of disease associated-loci between Europeans and East Asians are highly correlated with genetic differentiation between these populations. Finally, highly replicated genes present increased levels of high-frequency derived alleles in European and Asian populations when compared to African populations. Conclusions Our findings highlight the heterogeneous nature of the genetic etiology of complex disease, confirm the importance of the recent evolutionary history of our species in current patterns of disease susceptibility and could cast doubts on the status as false positives of some associations that have failed to replicate across populations.
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Affiliation(s)
- Urko M Marigorta
- Institute of Evolutionary Biology (UPF-CSIC), PRBB, Doctor Aiguader 88, 08003, Barcelona, Catalonia, Spain
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Ned RM, Yesupriya A, Imperatore G, Smelser DT, Moonesinghe R, Chang MH, Dowling NF. Inflammation gene variants and susceptibility to albuminuria in the U.S. population: analysis in the Third National Health and Nutrition Examination Survey (NHANES III), 1991-1994. BMC MEDICAL GENETICS 2010; 11:155. [PMID: 21054877 PMCID: PMC2991302 DOI: 10.1186/1471-2350-11-155] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/15/2010] [Accepted: 11/05/2010] [Indexed: 11/17/2022]
Abstract
BACKGROUND Albuminuria, a common marker of kidney damage, serves as an important predictive factor for the progression of kidney disease and for the development of cardiovascular disease. While the underlying etiology is unclear, chronic, low-grade inflammation is a suspected key factor. Genetic variants within genes involved in inflammatory processes may, therefore, contribute to the development of albuminuria. METHODS We evaluated 60 polymorphisms within 27 inflammatory response genes in participants from the second phase (1991-1994) of the Third National Health and Nutrition Examination Survey (NHANES III), a population-based and nationally representative survey of the United States. Albuminuria was evaluated as logarithm-transformed albumin-to-creatinine ratio (ACR), as ACR ≥ 30 mg/g, and as ACR above sex-specific thresholds. Multivariable linear regression and haplotype trend analyses were conducted to test for genetic associations in 5321 participants aged 20 years or older. Differences in allele and genotype distributions among non-Hispanic whites, non-Hispanic blacks, and Mexican Americans were tested in additive and codominant genetic models. RESULTS Variants in several genes were found to be marginally associated (uncorrected P value < 0.05) with log(ACR) in at least one race/ethnic group, but none remained significant in crude or fully-adjusted models when correcting for the false-discovery rate (FDR). In analyses of sex-specific albuminuria, IL1B (rs1143623) among Mexican Americans remained significantly associated with increased odds, while IL1B (rs1143623), CRP (rs1800947) and NOS3 (rs2070744) were significantly associated with ACR ≥ 30 mg/g in this population (additive models, FDR-P < 0.05). In contrast, no variants were found to be associated with albuminuria among non-Hispanic blacks after adjustment for multiple testing. The only variant among non-Hispanic whites significantly associated with any outcome was TNF rs1800750, which failed the test for Hardy-Weinberg proportions in this population. Haplotypes within MBL2, CRP, ADRB2, IL4R, NOS3, and VDR were significantly associated (FDR-P < 0.05) with log(ACR) or albuminuria in at least one race/ethnic group. CONCLUSIONS Our findings suggest a small role for genetic variation within inflammation-related genes to the susceptibility to albuminuria. Additional studies are needed to further assess whether genetic variation in these, and untested, inflammation genes alter the susceptibility to kidney damage.
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Affiliation(s)
- Renée M Ned
- Office of Public Health Genomics, Office of Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Ajay Yesupriya
- Office of Public Health Genomics, Office of Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Giuseppina Imperatore
- Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Diane T Smelser
- Office of Public Health Genomics, Office of Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention, Atlanta, GA, USA
- American Society of Human Genetics Fellow, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Ramal Moonesinghe
- Office of Minority Health and Health Disparities, Office of the Director, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Man-huei Chang
- Office of Public Health Genomics, Office of Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Nicole F Dowling
- Office of Public Health Genomics, Office of Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention, Atlanta, GA, USA
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Gadow KD, DeVincent CJ, Pisarevskaya V, Olvet DM, Xu W, Mendell N, Finch SJ, Hatchwell E. Parent-child DRD4 genotype as a potential biomarker for oppositional, anxiety, and repetitive behaviors in children with autism spectrum disorder. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34:1208-14. [PMID: 20600463 PMCID: PMC2939241 DOI: 10.1016/j.pnpbp.2010.06.019] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2010] [Revised: 06/21/2010] [Accepted: 06/22/2010] [Indexed: 01/26/2023]
Abstract
The primary objective of the present study was to examine whether a combination of parent-child DRD4 genotypes results in more informative biomarkers of oppositional, separation anxiety, and repetitive behaviors in children with autism spectrum disorder (ASD). Based on prior research indicating the 7-repeat allele as a potential risk variant, participants were sorted into one of four combinations of parent-child genotypes. Owing to the possibility of parent-of-origin effects, analyses were conducted separately for mother-child (MC) and father-child (FC) dyads. Mothers completed a validated DSM-IV-referenced rating scale. Partial eta-squared (ηp(2)) was used to determine the magnitude of group differences: 0.01-0.06=small, 0.06-0.14=moderate, and >0.14=large. Analyses indicated that children in MC dyads with matched genotypes had the least (7-/7-) and most (7+/7+) severe mother-rated oppositional-defiant (ηp(2)=0.11) and separation anxiety (ηp(2)=0.19) symptoms. Conversely, youths in FC dyads with matched genotypes had the least (7-/7-) and most (7+/7+) severe obsessive-compulsive behaviors (ηp(2)=0.19) and tics (ηp(2)=0.18). Youths whose parents were both noncarriers had less severe tics than peers with at least one parental carrier, and the effect size was large (ηp(2)=0.16). There was little evidence that noncarrier children were rated more severely by mothers who were carriers versus noncarriers. Transmission Disequilibrium Test analyses provided preliminary evidence for undertransmission of the 2-repeat allele in youths with more severe tics (p=0.02). Parent genotype may be helpful in constructing prognostic biomarkers for behavioral disturbances in ASD; however, findings are tentative pending replication with larger, independent samples.
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Affiliation(s)
- Kenneth D. Gadow
- Correspondence: Kenneth D. Gadow, Ph.D., Department of Psychiatry, Putnam Hall, South Campus State University of New York, Stony Brook, NY 11794-8790, Phone: (631) 632-8858, FAX: (631) 632-8953
| | - Carla J. DeVincent
- Department of Pediatrics, State University of New York at Stony Brook, Stony Brook, NY 11794-8788, Phone: (631) 632-3042, FAX: (631) 632-3021,
| | | | - Doreen M. Olvet
- Zucker Hillside Hospital, Psychiatry Research, North Shore – Long Island Jewish Health System, Glen Oaks, NY 11004,
| | - Wenjie Xu
- Department of Applied mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794-8088,
| | - Nancy Mendell
- Department of Applied mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794-8088,
| | - Stephen J. Finch
- Department of Applied mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794-8088,
| | - Eli Hatchwell
- Department of Pathology, Director of the Genomics Core Facility and Associate Professor, HSC-T8, Room 053, Stony Brook University, Stony Brook, NY 11794-8088, Phone: 631-444-1206, FAX: 631-444-3129,
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Yang YH, Li RN, Tzou SC, Wang JY, Lee HP, Wang HC, Chen FM, Wang YH, Hsieh MC, Huang MY, Tseng WL, Lin SR, Cheng TL. Simultaneous detection of multiple single-nucleotide polymorphisms by a simple membrane chip. Genet Test Mol Biomarkers 2010; 14:653-659. [PMID: 20858048 DOI: 10.1089/gtmb.2010.0032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Technologies that screen multiple single-nucleotide polymorphisms (SNPs) could be very valuable in predicting patients' susceptibilities to diseases or responses to therapeutic interventions. In this study, we developed a chip that can accurately detect four SNPs at same time. This chip is cost-effective and user-friendly because it uses a detection protocol analogous to dot blotting and does not require sophisticated instruments. To establish this chip, we designed and blotted onto a nylon membrane SNP-specific oligonucleotide probes for human angiotensinogen, cholesteryl ester transfer protein, and apolipoprotein E. This chip detected the corresponding SNPs harbored within the angiotensinogen, cholesteryl ester transfer protein, and apolipoprotein E sequences from 20 donors. Importantly, the SNPs detected by our chip matched exactly with the direct sequencing results, thereby highlighting the accuracy of this chip. In conclusion, our chip is a robust tool for multiple SNP screening and holds the potential to future refinement in detecting diseases-associating genes in patients.
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Affiliation(s)
- Yu-Hsiang Yang
- Graduate Institute of Medical Genetics, Kaohsiung Medical University, Kaohsiung, Taiwan
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Gadow KD, DeVincent CJ, Olvet DM, Pisarevskaya V, Hatchwell E. Association of DRD4 polymorphism with severity of oppositional defiant disorder, separation anxiety disorder and repetitive behaviors in children with autism spectrum disorder. Eur J Neurosci 2010; 32:1058-65. [DOI: 10.1111/j.1460-9568.2010.07382.x] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
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Royal CD, Novembre J, Fullerton SM, Goldstein DB, Long JC, Bamshad MJ, Clark AG. Inferring genetic ancestry: opportunities, challenges, and implications. Am J Hum Genet 2010; 86:661-73. [PMID: 20466090 PMCID: PMC2869013 DOI: 10.1016/j.ajhg.2010.03.011] [Citation(s) in RCA: 131] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2009] [Revised: 02/22/2010] [Accepted: 03/10/2010] [Indexed: 10/19/2022] Open
Abstract
Increasing public interest in direct-to-consumer (DTC) genetic ancestry testing has been accompanied by growing concern about issues ranging from the personal and societal implications of the testing to the scientific validity of ancestry inference. The very concept of "ancestry" is subject to misunderstanding in both the general and scientific communities. What do we mean by ancestry? How exactly is ancestry measured? How far back can such ancestry be defined and by which genetic tools? How do we validate inferences about ancestry in genetic research? What are the data that demonstrate our ability to do this correctly? What can we say and what can we not say from our research findings and the test results that we generate? This white paper from the American Society of Human Genetics (ASHG) Ancestry and Ancestry Testing Task Force builds upon the 2008 ASHG Ancestry Testing Summary Statement in providing a more in-depth analysis of key scientific and non-scientific aspects of genetic ancestry inference in academia and industry. It culminates with recommendations for advancing the current debate and facilitating the development of scientifically based, ethically sound, and socially attentive guidelines concerning the use of these continually evolving technologies.
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Affiliation(s)
- Charmaine D Royal
- Institute for Genome Sciences & Policy, Duke University, Durham, NC 27708, USA.
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Chee MWL, Zheng H, Goh JOS, Park D, Sutton BP. Brain structure in young and old East Asians and Westerners: comparisons of structural volume and cortical thickness. J Cogn Neurosci 2010; 23:1065-79. [PMID: 20433238 DOI: 10.1162/jocn.2010.21513] [Citation(s) in RCA: 92] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
There is an emergent literature suggesting that East Asians and Westerners differ in cognitive processes because of cultural biases to process information holistically (East Asians) or analytically (Westerners). To evaluate the possibility that such differences are accompanied by differences in brain structure, we conducted a large comparative study on cognitively matched young and old adults from two cultural/ethnic groups--Chinese Singaporeans and non-Asian Americans--that involved a total of 140 persons. Young predominantly White American adults were found to have higher cortical thickness in frontal, parietal, and medial-temporal polymodal association areas in both hemispheres. These findings were replicated using voxel-based morphometry applied to the same data set. Differences in cortical thickness observed between young volunteers were not significant in older subjects as a whole. However, group differences were evident when high-performing old were compared. Although the observed differences in gray matter may be rooted in strategic differences in cognition arising from ethnic/cultural differences, alternative explanations involving genetic heritage and environmental factors are also considered.
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Affiliation(s)
- Michael Wei Liang Chee
- Cognitive Neuroscience Laboratory, Duke-NUS Graduate Medical School, College Road, 7 Hospital Drive, Block B, 169857 Singapore, Singapore.
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Acquaviva KD, Mintz M. Perspective: are we teaching racial profiling? The dangers of subjective determinations of race and ethnicity in case presentations. ACADEMIC MEDICINE : JOURNAL OF THE ASSOCIATION OF AMERICAN MEDICAL COLLEGES 2010; 85:702-705. [PMID: 20354391 DOI: 10.1097/acm.0b013e3181d296c7] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/29/2023]
Abstract
Physicians make subjective visual assessments concerning the race and/or ethnicity of their patients and document these assessments in patient histories every day. Medical students learn this practice through textbooks and the example set by their educators. Although physicians may believe that they are helping their patients, the practice of using visual clues concerning race and/or ethnicity to determine whether a patient is at risk of certain diseases lacks scientific rigor and may put the patient at significant risk of receiving substandard medical care. The authors argue that if the patient's race or ethnicity is of critical importance, the data should be collected through more objective, scientifically rigorous means, such as genetic testing. In this article, the authors call for the widespread transformation of the way medical schools teach tomorrow's physicians about the role of race and ethnicity in taking medical histories, and they challenge physicians to change their current practices.
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Affiliation(s)
- Kimberly D Acquaviva
- Department of Nursing Education, The George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA.
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Haiman CA, Stram DO. Exploring genetic susceptibility to cancer in diverse populations. Curr Opin Genet Dev 2010; 20:330-5. [PMID: 20359883 DOI: 10.1016/j.gde.2010.02.007] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2010] [Revised: 02/09/2010] [Accepted: 02/20/2010] [Indexed: 01/15/2023]
Abstract
Incidence rates for many cancers differ markedly by race/ethnicity and furthering our understanding of the genetic and environmental causes of such disparities is a scientific and public health need. Genome-wide association studies (GWAS) are widely acknowledged to provide important information about the etiology of common cancers. To date, these studies have been primarily conducted in European-derived populations. There are important reasons for extending the reach of GWAS studies to other groups and for conducting multiethnic genetic studies involving multiple populations and admixed populations. These include a (1) need to discover the full scope of variants that affect risk of disease in all populations, (2) furthering the understanding of disease pathways, and (3) to assist in fine-mapping of genetic associations by exploiting the differences in linkage disequilibrium between populations to narrow the range of marker alleles demarking regions that contain a true biologically relevant variant. Challenges to multiethnic studies relating to study power, control for hidden population structure, imputation, and use of shared controls for multiple cancer endpoints are discussed.
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Affiliation(s)
- Christopher A Haiman
- Department of Preventive Medicine, Keck School of Medicine and the Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
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Chernin G, Heeringa SF, Vega-Warner V, Schoeb DS, Nürnberg P, Hildebrandt F. Adequate use of allele frequencies in Hispanics--a problem elucidated in nephrotic syndrome. Pediatr Nephrol 2010; 25:261-6. [PMID: 19876656 PMCID: PMC2899680 DOI: 10.1007/s00467-009-1315-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2009] [Revised: 08/13/2009] [Accepted: 08/13/2009] [Indexed: 01/19/2023]
Abstract
Previous studies in children with focal segmental glomerulosclerosis (FSGS) and nephrotic syndrome (NS) in the USA have revealed inter-ethnic differences in their clinical presentation and outcome. However, ethnicity was based on self-identification rather than on molecular genetic data. Here, we show that genetic heterogeneity exists in self-identified Hispanic (Spanish-American) patients with steroid-resistant nephrotic syndrome (SRNS), as patients may be either of Caucasian or Mesoamerican (Native-American) genetic background. Twenty-one self-identified Hispanic patients with SRNS from 18 families were initially evaluated for mutations in the NPHS2 and WT1 genes. All patients resided and were cared for in the USA. We performed a total genome search for linkage in all Hispanic patients using 250K single nucleotide polymorphism microarrays, comparing Caucasian with Mesoamerican allele frequencies to determine regions of homozygosity by descent and to establish the correct allele frequency for each family. We found that only ten families (56%) of the 18 self-identified Hispanic families are genetically of Mesoamerican descent, whereas the other eight families (44%) are of Caucasian descent. Due to the small number of families examined, we were unable to draw any conclusion on the prevalence of NPHS2 and WT1 in this ethnic group, but the data do suggest that self-identification of ethnicity in Hispanic-American patients is not an adequate basis for genetic studies, as this cohort may represent not only patients of Mesoamerican origin but also patients of Caucasian origin. Thus, one needs to critically review previous studies of FSGS/SRNS patients that involved Hispanic patients as a group. Future larger studies may employ a total genome search for linkage to test self-identified Hispanic ethnicity for true Mesoamerican versus Caucasian ethnicity in order to generate valid genetic data.
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Affiliation(s)
- Gil Chernin
- Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor, MI, USA
| | - Saskia F. Heeringa
- Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor, MI, USA
| | - Virginia Vega-Warner
- Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor, MI, USA
| | - Dominik S. Schoeb
- Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor, MI, USA
| | - Peter Nürnberg
- Center for Genomics (CCG) and Institute for Genetics, Universität zu Köln, Cologne, Germany
| | - Friedhelm Hildebrandt
- Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor, MI, USA. Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, USA. University of Michigan Health System, 8220C MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5646, USA
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Wassel CL, Pankow JS, Peralta CA, Choudhry S, Seldin MF, Arnett DK. Genetic ancestry is associated with subclinical cardiovascular disease in African-Americans and Hispanics from the multi-ethnic study of atherosclerosis. CIRCULATION. CARDIOVASCULAR GENETICS 2009; 2:629-36. [PMID: 20031644 PMCID: PMC2795643 DOI: 10.1161/circgenetics.109.876243] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
BACKGROUND Differences in cardiovascular disease (CVD) burden exist among racial/ethnic groups in the United States, with African-Americans having the highest prevalence. Subclinical CVD measures have also been shown to differ by race or ethnicity. In the United States, there has been a significant intermixing among racial/ethnic groups creating admixed populations. Very little research exists on the relationship of genetic ancestry and subclinical CVD measures. METHODS AND RESULTS These associations were investigated in 712 black and 705 Hispanic participants from the Multi-Ethnic Study of Atherosclerosis candidate gene substudy. Individual ancestry was estimated from 199 genetic markers using STRUCTURE. Associations of ancestry and coronary artery calcium (CAC) and common and internal carotid intima media thickness were evaluated using log-binomial and linear regression models. Splines indicated linear associations of ancestry with subclinical CVD measures in African-Americans but presence of threshold effects in Hispanics. Among African-Americans, each SD increase in European ancestry was associated with an 8% (95% CI, 1.02 to 1.15; P=0.01) higher CAC prevalence. Each SD increase in European ancestry was also associated with a 2% (95% CI -3.4% to -0.5%, P=0.008) lower common carotid intima media thickness in African-Americans. Among Hispanics, the highest tertile of European ancestry was associated with a 34% higher CAC prevalence (P=0.02) when compared with the lowest tertile. CONCLUSIONS The linear association of ancestry and subclinical CVD suggests that genetic effects may be important in determining CAC and carotid intima media thickness among African-Americans. Our results also suggest that CAC and common carotid intima media thickness may be important phenotypes for further study with admixture mapping.
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Affiliation(s)
- Christina L Wassel
- Department of Family and Prevention Medicine, University of California, San Diego, CA 92093-0965, USA.
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Bonham VL, Knerr S, Feero WG, Stevens N, Jenkins JF, McBride CM. Patient physical characteristics and primary care physician decision making in preconception genetic screening. Public Health Genomics 2009; 13:336-44. [PMID: 19940457 DOI: 10.1159/000262328] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/06/2009] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND There has been growing emphasis on preconception care as a strategy to improve maternal and child health since the 1980s. Increasingly, development of genetic tests will require primary care providers to make decisions about preconception genetic screening. Limited research has been conducted on how primary care providers interpret patients' characteristics and use constructs, such as ethnicity and race, to decide whom to offer preconception genetic screening. OBJECTIVE This report assessed the influence of patient characteristics on decisions to offer preconception genetic screening. METHODS A web-based survey of family physicians was conducted. Physicians reviewed a clinical vignette that was accompanied by a picture of either a black or a white patient. Physicians indicated whether they would offer genetic screening, and if yes, what tests they would offer and what factors influenced their decisions. RESULTS The majority (69.2%) of physicians reported that they would not offer genetic screening. Respondents who reviewed the vignette accompanied by a picture of the black patient were more likely to offer screening (35% vs. 26%, p = 0.0034) and rated race as more important to their decision to offer testing than those who viewed the picture of the white patient (76% vs. 49%, p < 0.0001). CONCLUSIONS Our findings suggest that patient race is important to physicians when making decisions about preconception genetic testing and that decision making is influenced by patients' physical characteristics. The reticence of physicians in this sample to offer preconception screening is an important finding for public health and clinical practice.
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Affiliation(s)
- V L Bonham
- Social and Behavioral Research Branch, National Human Genome Research Institute, NIH, Bethesda, Md. 20892-2152, USA.
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Klimentidis YC, Miller GF, Shriver MD. Genetic admixture, self-reported ethnicity, self-estimated admixture, and skin pigmentation among Hispanics and Native Americans. AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY 2009; 138:375-83. [PMID: 18951390 DOI: 10.1002/ajpa.20945] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The relationship between ethnicity and biology is of interest to anthropologists, biomedical scientists, and historians in understanding how human groups are constructed. Ethnic self-identification in recently admixed groups such as Hispanics, African Americans, and Native Americans (NA) is likely to be complex due to the heterogeneity in individual admixture proportions and social environments within these groups. This study examines the relationships between self-identified ethnicity, self-estimated admixture proportions, skin pigmentation, and genetic marker estimated admixture proportions. These measures were assessed using questionnaires, skin color measurements, and genotyping of a panel of 76 ancestry informative markers, among 170 Hispanics and NAs from New Mexico, a state known for its complex history of interactions between people of NA and European (EU) ancestry. Results reveal that NAs underestimate their degree of EU admixture, and that Hispanics underestimate their degree of NA admixture. Within Hispanics, genetic-marker estimated admixture is better predicted by forehead skin pigmentation than by self-estimated admixture. We also find that Hispanic individuals self-identified as "half-White, half Hispanic" and "Spanish" have lower levels of NA admixture than those self-identified as "Mexican" and "Mexican American." Such results highlight the interplay between culture and biology in how individuals identify and view themselves, and have implications for how ethnicity and disease risk are assessed in a medical setting.
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Affiliation(s)
- Yann C Klimentidis
- Department of Anthropology, University of New Mexico, Albuquerque, NM 87130, USA.
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Block R, Corsetti J, Goldenberg I, Vorobiof G, McNitt S, Ryan D, Zareba W, Moss AJ. The common apolipoprotein A-1 polymorphism -75A>G is associated with ethnic differences in recurrent coronary events after recovery from an acute myocardial infarction. Heart Int 2009; 4:e8. [PMID: 21152377 PMCID: PMC2997744 DOI: 10.4081/hi.2009.e8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2009] [Accepted: 10/05/2009] [Indexed: 11/22/2022] Open
Abstract
Since data regarding the relationship between a common polymorphism (SNP) of the apoA1 gene with apoA1 levels and risk of coronary artery disease are inconsistent, we hypothesized that its association with recurrent coronary events differs for White and Black individuals with diagnosed coronary heart disease. The apoA1 -75G>A SNP was genotyped in a cohort of 834 Black (n=129) and White (n=705) post-myocardial infarction patients. Recurrent coronary events (coronary-related death, non-fatal myocardial infarction, or unstable angina) were documented during an average follow-up of 28 months. Thirty percent of White and 21% of Black patients carried the SNP. Cox proportional-hazards regression analysis, adjusting for clinical and laboratory covariates, demonstrated that the SNP was not associated with recurrent events in the total cohort (HR=1.37, 95% CI 0.95-1.97; p= 0.09) but was the only variable associated with an increased risk of recurrent cardiac events in Blacks (HR=2.40, 95% CI 1.07-5.40; p= 0.034). Conversely in Whites, the SNP was not associated with recurrent events (HR=1.12, 95% CI 0.75-1.67; p= 0.59) whereas apoB (HR=1.78, 95% CI 1.20 -2.65; p= 0.0042) and calcium channel blocker use (HR=2.53, 95% CI 1.72-3.72; p<0.001) were associated; p= 0.0024 for interaction between ethnicity and the SNP. A common apoA1 SNP is associated with a significantly increased risk of recurrent cardiac events among Black, but not White, postmyocardial infarction patients. Relationships with lipoproteins may help explain this finding.
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Affiliation(s)
- Robert Block
- Department of Community and Preventive Medicine, University of Rochester, Rochester, NY
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Curry WT, Barker FG. Racial, ethnic and socioeconomic disparities in the treatment of brain tumors. J Neurooncol 2009; 93:25-39. [PMID: 19430880 DOI: 10.1007/s11060-009-9840-5] [Citation(s) in RCA: 114] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2008] [Accepted: 02/23/2009] [Indexed: 01/02/2023]
Abstract
Disparities in American health care based on socially-defined patient characteristics such as race, ethnicity, and socioeconomic position are well-documented. We review differences and disparities in incidence, pathobiology, processes and outcomes of care, and survival based on social factors for brain tumors of all histologies. In the US, black patients have lower incidences of most brain tumor types and lower-income patients have lower incidences of low grade glioma, meningioma and acoustic neuroma; ascertainment bias may contribute to these findings. Pathogenetic differences between malignant gliomas in patients of different races have been demonstrated, but their clinical significance is unclear. Patients in disadvantaged groups are less often treated by high-volume providers. Mortality and morbidity of initial treatment are higher for brain tumor patients in disadvantaged groups, and they present with markers of more severe disease. Long term survival differences between malignant glioma patients of different races have not yet been shown. Clinical trial enrollment appears to be lower among brain tumor patients from disadvantaged groups. We propose future research both to better define disparities and to alleviate them.
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Affiliation(s)
- William T Curry
- Department of Surgery (Neurosurgery), Pappas Center for Neuro-Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
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