Psychotropic Drug-Induced Lipid Disturbances: a Genome-Wide Association Study in a Swiss Psychiatric Cohort

Dyslipidemia affects patients with severe mental illness to varying degrees, partly due to medication side effects and genetic variations that modify drug-induced lipid changes. To identify these genetics contributors, we conducted a genome-wide association study (GWAS) on 829 patients of the PsyMetab cohort whose total-, LDL-, HDL- cholesterol and triglyceride levels were recorded pre- and up to one-year post psychotropic treatment. Seven different loci were associated at genome wide significance level (P < 5 × 10−8) with treatment-induced lipids changes. Three genetic variants were associated with total cholesterol change following aripiprazole, quetiapine, and combination of quetiapine, olanzapine, clozapine treatment (rs17313064 G > A, rs12543987 G > A, rs58331124 G > A, respectively). Two markers were associated with HDL-cholesterol change following lithium and mirtazapine treatment (rs12097296 C > T, rs10933971 C > T, respectively). One variant was associated with triglycerides change following risperidone treatment (rs10260518 G > T) and finally one genetic variation was associated with triglycerides change considering any drug treatment (rs56286230 T > G). To compensate for the lack of classical replication, sensitivity analyses were conducted by assessing the robustness of effects using different post-treatment interval lengths. Notably rs10933971 effect on HLD-cholesterol was consistently found across different patients and time-frames. These findings point to genes previously associated with total lipids level in the general population and highlight novel drug-specific associations which provide promising insights toward personalized psychotropic therapy.