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

Chapleau, Richard R

doi:10.1101/2022.12.12.22283345

Cited by 2 publications

(2 citation statements)

References 40 publications

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“…As with the prior study [6], this study was reviewed and approved by WCG IRB (Study number 1332892) and was performed in accordance with the Helsinki declaration. Data were obtained from the National Institutes of Health's Database of Genotypes and Phenotypes (dbGAP) using the Coronary Artery Risk Development in Young Adults (CARDIA) Study (dbGAP study accession phs000285) [8].…”

Section: Methodsmentioning

confidence: 99%

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Toward Understanding Genetic Risk of Burnout through Genome-wide Associations of Cynicism and Cynical Distrust

Chapleau¹

2023

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Cynicism is an attitude that people are motivated primarily by self-interest, and often manifests alongside emotions like contempt, anger, and hostility. Cynicism can impact all aspects of an individual's life: in the workplace it is a critical component of burnout, while at home it often leads to marital dissatisfaction and increased family conflicts. Using data from 2,317 participants in the CARDIA Cohort study, we performed a genome-wide association study (GWAS) to identify genetic variants related to cynicism and the cynical distrust sub-trait. We performed two GWAS tests for each trait, one without controlling for population stratification and a second where we considered possible ancestry-related stratification using principal component analysis within plink 1.9. We also tested multiple genetic inheritance models. Finally, we performed pathway analysis using the STRINGdb web resource to identify meaningful relationships. From our various approaches, we identified 12 variants associated with high cynicism in an additive model and 258 in a genotypic model. We also identified 24 and 275 variants associated with cynical distrust using the respective models. Our network analysis revealed clear pathways for how cynicism can lead to health outcomes like cardiovascular disease, adrenal disorders, neurological disorders, and even addiction. Specifically, genes involved in 30 distinct KEGG pathways were related to cynicism and clear connections can be made between cynicism and cardiomyopathies, Cushing syndrome, Alzheimer's disease, and amphetamine addiction. Each of the outcomes are supported by gene association with at least 3 intermediate pathways. Our results provide the first objective evidence supporting the observational literature connections to cardiovascular disease, Alzheimer's disease, and addiction. To the best of our knowledge, this is the first evidence presenting a relationship between cynicism and Cushing's syndrome, demonstrating the power of population and statistical genetics.

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Section: Methodsmentioning

confidence: 99%

“…To date, genetic risk markers for cynicism have only recently been reported [6], despite the inclusion of the CMHS in large scale genomics studies [7,8]. Genetic risk markers for cynicism may be able to serve as additional pieces of information regarding life-long physical and mental health outcomes.…”

Section: Introductionmentioning

confidence: 99%

Toward Understanding Genetic Risk of Burnout through Genome-wide Associations of Cynicism and Cynical Distrust

Chapleau¹

2023

Preprint

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Genome-wide association study of John Henryism in the CARDIA Cohort suggests a molecular mechanism behind lower nicotine addiction rates

Chapleau¹

2023

Preprint

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John Henryism (JH) is a stress response mechanism that enables individuals to cope with chronic psychological stressors. Originally identified in African American males, JH has since been associated with numerous negative health outcomes such as cardiovascular disease. Despite its relationship to diseases with known genetic risk factors, little work has been reported concerning the genetics of JH. In the current study, genome-wide microarray and the JH Active Coping scale data from the CARDIA Cohort study were used to identify genetic factors associated with JH levels. Principal component analysis accounted for population stratification and evaluated six inheritance models in plink software. We also performed network analyses on the resulting significant associations (P < 5x10-8) to identify molecular pathways to health outcomes. Our GWAS results revealed 25 significant genetic associations and two suggestive associations. One of the variants identified with a suggestive association (P < 5x10-6) to JH (rs11634680) reproduces the same suggestive association from a prior study of the same dataset with the similar odds ratios and P-values between the studies. In our pathway analysis, we found a variant associated with JH (rs12448959) decreases the amount of GABA transaminase and thereby reduces the nicotine reward through the GABAergic signaling pathway. Our work provides a molecular explanation to the observational data that individuals with high levels of JH active coping skills are less prone to using smoking as stress relief.

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

Cited by 2 publications

References 40 publications

Toward Understanding Genetic Risk of Burnout through Genome-wide Associations of Cynicism and Cynical Distrust

Toward Understanding Genetic Risk of Burnout through Genome-wide Associations of Cynicism and Cynical Distrust

Genome-wide association study of John Henryism in the CARDIA Cohort suggests a molecular mechanism behind lower nicotine addiction rates

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