Personality disorders and cardiometabolic diseases: A Mendelian randomization study

Area of Science:

• Genetics
• Psychiatry
• Cardiology

Background:

• Observational studies suggest links between personality disorders (PDs) and cardiometabolic diseases (CMDs).
• These associations may be confounded by lifestyle factors or reverse causality.
• Mendelian randomization (MR) offers a method to infer causality using genetic variants.

Purpose of the Study:

• To use MR to investigate the causal relationships between 9 PDs and 8 CMDs.
• To clarify previously observed epidemiological associations using genetic evidence.
• To differentiate biological causation from environmental or behavioral confounding.

Main Methods:

• Utilized MR with genetic variants as instrumental variables for 9 PDs (FinnGen) and 8 CMDs (UK Biobank).
• Selected single-nucleotide polymorphisms at genome-wide significance (P < 5 × 10⁻⁶) and clumped for independence (R² < 0.001).
• Employed inverse-variance weighted regression for primary estimates and sensitivity analyses (MR-Egger, Cochran Q, leave-one-out) for robustness.

Main Results:

• Genetically predicted organic personality disorder was positively associated with coronary atherosclerosis (OR = 1.001, P = 0.029).
• No other significant causal associations were detected between the studied PDs and CMDs (P > 0.05).
• Findings remained stable across sensitivity analyses.

Conclusions:

• The study's genetic evidence contrasts with prior observational findings for most PD-CMD links.
• Reported associations may stem from residual confounding by environmental or behavioral factors, not direct biological causation.
• Future research should explore behavioral and environmental mediators of epidemiological correlations between PDs and CMDs.