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
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:
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.
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

John Henryism (JH) is a strategy for dealing with chronic psychological stress characterized by high levels of physical effort and work. Cynicism is a belief that people are motivated primarily by self-interest. High scores on the JH scale and cynicism measures correlate with an increased risk of cardiovascular disease. High cynicism is also a hallmark of burnout syndrome, another known risk factor for heart disease.


To evaluate possible interactions between JH and cynicism hoping to clarify risk factors of burnout.


We analyzed genetic and psychological data available from the Database of Genotypes and Phenotypes for genome-wide associations with these traits. We split the total available samples and used plink to perform the association studies on the discovery set (n = 1852, 80%) and tested for replication using the validation set (n = 465). We used scikit-learn to perform supervised machine learning for developing genetic risk algorithms.


We identified 2, 727, and 204 genetic associations for scores on the JH, cynicism and cynical distrust (CD) scales, respectively. We also found 173 associations with high cynicism, 109 with high CD, but no associations with high JH. We also produced polygenic classifiers for high cynicism using machine learning with areas under the receiver operator characteristics curve greater than 0.7.


We found significant genetic components to these traits but no evidence of an interaction. Therefore, while there may be a genetic risk, JH is not likely a burnout risk factor.

Keywords: Cynicism, Burnout syndrome, John Henryism, Genome-wide association study, Polygenic risk score, Machine-learning

Core Tip: This study evaluates the interaction of a job-related cardiovascular disease risk factor (John Henryism) and the development of occupational burnout (specifically the cynicism and cynical distrust components). Genome-wide associations and statistical genetics revealed that while John Henryism is not a risk factor for burnout syndrome, there are independent genetic risk factors for both John Henryism and cynicism. These new results provide additional tools to industrial and occupational psychologists, as well as cardiologists, to help reduce burnout incidence.