serval:BIB_FB1D5A1CCA6F
Influence of polygenic risk scores on lipid levels and dyslipidemia in a psychiatric population receiving weight gain-inducing psychotropic drugs.
10.1097/FPC.0000000000000313
000418362600005
28945215
Delacrétaz
A.
author
Lagares Santos
P.
author
Saigi Morgui
N.
author
Vandenberghe
F.
author
Glatard
A.
author
Gholam-Rezaee
M.
author
von Gunten
A.
author
Conus
P.
author
Eap
C.B.
author
article
2017-12
Pharmacogenetics and genomics
1744-6880
1744-6872
journal
27
12
464-472
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.
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.
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).
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.
eng
60_published
true
peer-reviewed
Publication types: Journal Article
Publication Status: ppublish
University of Lausanne
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