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Influence of polygenic risk scores on lipid levels and dyslipidemia in a psychiatric population receiving weight gain-inducing psychotropic drugs

Objectives Dyslipidemia represents a major health issue in psychiatry. We determined whether weighted polygenic risk scores (wPRSs) combining multiple single-nucleotide polymorphisms (SNPs) associated with lipid levels in the general population are associated with lipid levels [high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol (TC), and triglycerides] and/or dyslipidemia in patients receiving weight gain-inducing psychotropic drugs. We also determined whether genetics improve the predictive power of dyslipidemia. Patients and methods The influence of wPRS on lipid levels was firstly assessed in a discovery psychiatric sample (n=332) and was then tested for replication in an independent psychiatric sample (n=140). The contribution of genetic markers to predict dyslipidemia was evaluated in the combined psychiatric sample. Results wPRSs were significantly associated with the four lipid traits in the discovery (P⩽0.02) and in the replication sample (P⩽0.03). Patients whose wPRS was higher than the median wPRS had significantly higher LDL, TC, and triglyceride levels (0.20, 0.32 and 0.26 mmol/l, respectively; P⩽0.004) and significantly lower HDL levels (0.13 mmol/l; P<0.0001) compared with others. Adding wPRS to clinical data significantly improved dyslipidemia prediction of HDL (P=0.03) and a trend for improvement was observed for the prediction of TC dyslipidemia (P=0.08). Conclusion Population-based wPRSs have thus significant effects on lipid levels in the psychiatric population. As genetics improved the predictive power of dyslipidemia development, only 24 patients need to be genotyped to prevent the development of one case of HDL hypocholesterolemia. If confirmed by further prospective investigations, the present results could be used for individualizing psychotropic treatment.