Psychotropic drug-induced lipid disturbances: a genome-wide association study in a Swiss psychiatric cohort

Vollständiger Abstract

Worum geht es in dieser Arbeit?

Abstract 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.