Genetically predicted higher neuroticism was causally associated with reduced cardiomyopathy risk (OR 0.85-0.88, P<0.05), partially mediated by circulating proteins.
Observational
Mendelian randomization
Yes
Does genetically predicted higher neuroticism reduce the risk of cardiomyopathy?
Genetically predicted higher neuroticism is causally linked to a lower risk of primary cardiomyopathy, partially mediated by circulating proteins.
Effect estimate: OR 0.85-0.88
p-value: p=<0.05
BACKGROUND The relationship between Neuroticism and cardiomyopathy (CM) remains underexplored, despite links to other cardiovascular conditions. OBJECTIVES To investigate the causal effect of genetically predicted neuroticism on cardiomyopathy risk and to identify circulating protein mediators of this association using a two-step, proteome-wide mediation Mendelian randomization (MR) framework. METHODS We performed a two-sample MR study using GWAS data from UK Biobank (neuroticism: n = 393,411-374,323) and FinnGen (cardiomyopathy: n = 159,811-218,792). Causal estimates were derived using inverse-variance weighted MR, with sensitivity, multivariable MR, reverse-direction MR, and proteome-wide two-step mediation MR to identify circulating protein mediators. RESULTS Genetically predicted higher neuroticism was causally associated with reduced cardiomyopathy risk (IVW OR = 0.85-0.88, P 0.05), thereby supporting the robustness of the findings. CONCLUSIONS Our findings provide genetic evidence that higher neuroticism is causally linked to a lower risk of primary (nonischemic) cardiomyopathy, partially mediated by circulating proteins involved in immune, hematopoietic, and neuroendocrine pathways.
Wang et al. (2026) conducted an observational in Cardiomyopathy. Genetically predicted higher neuroticism was evaluated on Cardiomyopathy risk (OR 0.85-0.88, p=<0.05). Genetically predicted higher neuroticism was causally associated with reduced cardiomyopathy risk (OR 0.85-0.88, P<0.05), partially mediated by circulating proteins.