Genome-wide Associations, Polygenic Risk, and Mendelian Randomization Reveal Limited Interactions between John Henryism and Cynicism

Chronic occupational stress and an individual's reaction to that stress often lead to burnout syndrome. We sought to use genetics to evaluate what, if any, interactions exist between John Henryism (JH) and cynicism in hopes of clarifying holistic risk factors of burnout syndrome. We performed genome-wide association studies in a discover phase with 1,852 samples and validated associations in a replication phase of 465 samples, both from the CARDIA study, and used supervised machine learning to developing genetic risk algorithms. We identified 933 genetic associations and developed a classification algorithm 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 between JH and cynicism, so while there may be a genetic risk component, JH does not appear to contribute to burnout risk.