Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Med Genet. Jun 2, 2023; 11(2): 8-20
Published online Jun 2, 2023. doi: 10.5496/wjmg.v11.i2.8
Genome-wide associations, polygenic risk, and Mendelian randomization reveal limited interactions between John Henryism and cynicism
Richard R Chapleau
Richard R Chapleau, Department of Genetics, NeuroStat Analytical Solutions, Great Falls, VA 22066, United States
Author contributions: The author confirms sole responsibility for the following: study conception and design, data collection, analysis and interpretation of results, and manuscript preparation.
Institutional review board statement: The study was reviewed and approved by the WIRB-Copernicus Group Institutional Review Board (Protocol Number: 1332892).
Conflict-of-interest statement: The author declares no conflict of interest.
Data sharing statement: Summary statistics for significant variants are available from the corresponding author at richard.chapleau@nsas-llc.com.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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 NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Richard R Chapleau, PhD, Senior Scientist, Department of Genetics, NeuroStat Analytical Solutions, 1142 Walker Rd Suite H, Great Falls, VA 22066, United States. richard.chapleau@nsas-llc.com
Received: February 8, 2023
Peer-review started: February 8, 2023
First decision: April 28, 2023
Revised: April 28, 2023
Accepted: May 22, 2023
Article in press: May 22, 2023
Published online: June 2, 2023
Processing time: 113 Days and 11.9 Hours
ARTICLE HIGHLIGHTS
Research background

Our hypothesis was that cynicism, a distrustful attitude that assumes people are mainly driven by self-interest, would result from John Henryism (JH), a coping strategy that involves working hard and exerting high levels of effort to deal with chronic stress. We reasoned that as JH is a way of handling discrimination, and that cynicism involves skepticism and negativity towards others, the two traits would be related. Furthermore, both JH and cynicism are linked to a higher risk of cardiovascular disease, while cynicism also often accompanies burnout syndrome, another cardiovascular risk factor.

Research motivation

Rates of burnout are increasing broadly across the globe. Burnout can cause physiological and emotional distress. Understanding the role of stress coping skills such as JH may help clarify the role of occupational stress in overall health and well-being.

Research objectives

The present study aimed to determine if JH is correlated with the cynicism component of burnout by using approaches from statistical genetics.

Research methods

Genotype and phenotype data from the “CARDIA Cohort” study were obtained from the Database of Genotypes and Phenotypes. Genome-wide association studies (GWAS) were performed in plink version 1.9 on the log-normalized JH, cynicism, and cynical distrust (CD) phenotypes as well as a binary “high/Low” trait for each phenotype using a two-stage discovery and replication approach. The GWAS results were then used to develop polygenic risk score (PRS) algorithms using supervised machine learning in scikit-learn. Significant variants identified in the discovery stage were tested for replication by performing GWAS in a second, independent set of data restricting variants only to those candidates identified in discovery (for continuous variables) or through chi-square testing for the binary variable. The performance of the PRS algorithms at classifying individuals as “high” or “low” for the phenotype was evaluated in scikit-learn using the area under the receiver operator characteristics curve.

Research results

The GWAS identified significant variant associations with JH (2), cynicism (727), or CD (204) scores and with high cynicism (173) or CD (109). PRS classifiers were successfully developed for cynicism and CD (AUC > 0.65), but not for JH. Neither of the classifiers for cynicism or CD could predict JH traits, nor could the JH classifier predict cynicism or CD.

Research conclusions

There are genetic variants associated with each trait, however JH active coping does not appear to be correlated with cynicism or CD levels.

Research perspectives

The genetic associations with these phenotypes suggest that further research could provide insight into how each trait results in health impacts such as cardiovascular disease.