Observational Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Nov 15, 2019; 10(11): 534-545
Published online Nov 15, 2019. doi: 10.4239/wjd.v10.i11.534
Type 1 diabetes loci display a variety of native American and African ancestries in diseased individuals from Northwest Colombia
Natalia Gomez-Lopera, Juan M Alfaro, Suzanne M Leal, Nicolas Pineda-Trujillo
Natalia Gomez-Lopera, Juan M Alfaro, Nicolas Pineda-Trujillo, Grupo Mapeo Genetico, Departamento de Pediatría, Facultad de Medicina, Universidad de Antioquia, Medellín 050010470, Colombia
Juan M Alfaro, Sección de Endocrinología Pediátrica, Departamento de Pediatría, Facultad de Medicina, Universidad de Antioquia, Medellín 050010470, Colombia
Suzanne M Leal, Center for Statistical Genetics, Columbia University, New York, NY 10032, United States
Author contributions: Alfaro JM and Pineda-Trujillo N designed and coordinated the study; Gomez-Lopera N performed most of the data analyses; Pineda-Trujillo N and Leal SM wrote the manuscript.
Supported by Colciencias-Colombia grant No. 111556933366 and CODI-Universidad de Antioquia, and Scholarship from Colciencias, call No. 727 (from 2015).
Institutional review board statement: The ethics committee of the Medical Research Institute of the Medicine Faculty at University of Antioquia considers that the project does not contain ethical tensions that violate the rights and welfare of the participants. The risk involved in the study is minimum.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: None to declare.
STROBE statement: We have read the STROBE Guidelines, and the manuscript was prepared and revised according to them.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Nicolas Pineda-Trujillo, MSc, PhD, Academic Research, Research Scientist, Senior Scientist, Grupo Mapeo Genetico, Departamento de Pediatría, Facultad de Medicina, Universidad de Antioquia, Carrera 51D No. 62-21, Medellín 050010470, Colombia. nicolas.pineda@udea.edu.co
Telephone: +57-4-2196065 Fax: +57-4-2196069
Received: July 18, 2019
Peer-review started: July 21, 2019
First decision: August 31, 2019
Revised: September 10, 2019
Accepted: October 7, 2019
Article in press: October 7, 2019
Published online: November 15, 2019
Processing time: 108 Days and 3.6 Hours
Abstract
BACKGROUND

Type 1 diabetes (T1D) is a complex disease with a higher incidence in Europeans than other populations. The Colombians Living in Medellin (CLM) is admixed with ancestry contributions from Europeans, Native Americans (NAT) and Africans (AFR).

AIM

Our aim was to analyze the genetic admixture component at candidate T1D loci in Colombian individuals with the disease.

METHODS

Seventy-four ancestry informative markers (AIMs), which tagged 41 T1D candidate loci/genes, were tested by studying a cohort of 200 Northwest Colombia diseased individuals. T1D status was classified by testing for glutamic acid decarboxylase (GAD-65 kDa) and protein tyrosine-like antigen-2 auto-antibodies in serum samples. Candidate loci/genes included HLA, INS, PTPN22, CTLA4, IL2RA, SUMO4, CLEC16A, IFIH1, EFR3B, IL7R, NRP1 and RNASEH1, amongst others. The 1,000 genome database was used to analyze data from 94 individuals corresponding to the reference CLM. As the data did not comply with a normal distribution, medians were compared between groups using the Mann-Whitney U-test.

RESULTS

Both T1D patients and individuals from CLM displayed mainly European ancestry (61.58 vs 62.06) followed by Native American (27.34 vs 27.46) and to a lesser extent the AFR ancestry (10.28 vs 10.65) components. However, compared to CLM, ancestry of T1D patients displayed a decrease of NAT ancestry at gene EFR3B (24.30 vs 37.10) and an increase at genes IFIH1 (32.07 vs 14.99) and IL7R (52.18 vs 39.18). Also, for gene NRP1 (36.67 vs 0.003), we observed a non-AFR contribution (attributed to NAT). Autoimmune patients (positive for any of two auto-antibodies) displayed lower NAT ancestry than idiopathic patients at the MHC region (20.36 vs 31.88). Also, late onset patients presented with greater AFR ancestry than early onset patients at gene IL7R (19.96 vs 6.17). An association analysis showed that, even after adjusting for admixture, an association exists for at least seven such AIMs, with the strongest findings on chromosomes 5 and 10 (gene IL7R, P = 5.56 × 10-6 and gene NRP1, P = 8.70 × 10-19, respectively).

CONCLUSION

Although Colombian T1D patients have globally presented with higher European admixture, specific T1D loci have displayed varying levels of Native American and AFR ancestries in diseased individuals.

Keywords: Type 1 diabetes; Genetic admixture; Native American; Idiopathic; Colombia

Core tip: We have tested the effect of genetic admixture in a set of Colombian patients with Type 1 Diabetes (T1D). We show that, although no differences between T1Ds and Colombians living in Medellin arose globally, there appear to be ancestry differences when looking at specific T1D loci/genes (e.g., genes EFR3B, IFIH1, IL7R and NRP1). Also, when comparing patient ancestry according to the presence/absence of T1D-related auto-antibodies or age at onset of the disease, differences were also observed. The most striking differences in ancestry occurred outside the HLA region, which is considered the master risk locus in T1D and for autoimmune diseases overall. This in itself is a striking observation.