Neuroticism as a protective factor for cardiomyopathy: A mediation Mendelian randomization study
Mengmeng Wang1, Tianqi Teng1, Degang Mo1
1Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, Shandong, China.
Journal of Affective Disorders
|February 22, 2026
Summary
Higher neuroticism (a personality trait) is genetically linked to a reduced risk of cardiomyopathy. This protective effect is partly explained by specific circulating proteins.
Area of Science:
- Cardiovascular Genetics
- Psychiatric Genomics
- Proteomics
Background:
- The link between neuroticism and cardiovascular disease is not fully understood.
- Cardiomyopathy (CM) specifically lacks exploration regarding neuroticism's influence.
Purpose of the Study:
- To determine if neuroticism causally affects cardiomyopathy risk.
- To identify proteins that mediate the relationship between neuroticism and CM using Mendelian randomization (MR).
Main Methods:
- A two-sample Mendelian randomization (MR) study utilized genome-wide association study (GWAS) data.
- Data sources included UK Biobank for neuroticism and FinnGen for cardiomyopathy.
- Proteome-wide mediation analysis identified mediating circulating proteins.
Main Results:
- Genetically predicted higher neuroticism showed a causal association with reduced cardiomyopathy risk (OR=0.85-0.88).
- Thirteen circulating proteins were identified as significant mediators of this protective effect.
- Higher neuroticism correlated with increased protein levels, which were linked to lower CM risk.
Conclusions:
- Genetic evidence supports a causal link between higher neuroticism and decreased primary cardiomyopathy risk.
- This association is partially mediated by circulating proteins in immune, hematopoietic, and neuroendocrine pathways.
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