Genetic variation mediating neuroticism’s influence on cardiovascular diseases.

Abstract

The personality of neuroticism is phenotypically associated with cardiovascular diseases (CVD), but the underlying mechanisms are poorly understood. We conducted Mendelian randomization analysis to investigate causal relationships between neuroticism and CVD (including coronary artery disease, heart failure, atrial fibrillation, stroke, and hypertensive disease) using summary results of genome-wide association studies for these traits. Our results show that although neuroticism has low or minimal correlations with CVD in general, there are substantial polygenic overlaps between neuroticism and CVD (20%$97%). Mendelian randomization analysis indicates that genetic liability to neuroticism exerts causal effects on CVD, but not the reverse. A panel of pleiotropic genes is shared by neuroticism and CVD, pointing to the potential role of the SOX-WNT/b-catenin-T-cell-specific transcription factors/ lymphoid enhancer factors pathway. Our study suggests that genetics may mediate the influence of neuroticism on CVD. The results shed light on mechanisms underlying phenotypic relationships between neuroticism and CVD and have implications for personalized prevention of CVD with the potential benefits of incorporating personality management into the treatment regimen. General Scientific SummaryOur results show that there are substantial polygenic overlaps between neuroticism and cardiovascular diseases. Genetic liability to neuroticism may exert causal effects on cardiovascular diseases, but not the reverse.

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