Bidirectional genetic overlap between psychiatric disorders and high-density lipoprotein cholesterol levels

Individuals with psychiatric disorders can show differences in plasma high-density lipoprotein cholesterol (HDL-C), although whether they share a common genomic basis is unclear. This study relied on publicly summarized data from genome-wide association studies for HDL-C and major psychiatric disorders to evaluate shared genetic architecture. Correlation between traits was summarized via linkage disequilibrium score regression. Using a bivariate causal mixture model, polygenicity was quantified alongside sharing versus trait-specificity. Jointly associated loci were mapped with a conjunctional false discovery rate approach. Analyses indicated polygenic overlap between HDL-C and several psychiatric disorders; the pattern differed across disorders. Mapped signals were primarily noncoding in available annotations, consistent with regulatory mechanisms. These findings did not establish causality or immediate clinical utility. They were compatible with attention to metabolic health in psychiatric care when clinically indicated and motivated prospective validation across diverse populations to support equitable applicability and clarify clinical significance.