Genome-wide association study identifies genetic loci associated with body mass index and high density lipoprotein-cholesterol levels during psychopharmacological treatment - a cross-sectional naturalistic study.

Metabolic and cardiovascular side effects are serious clinical problems related to psychopharmacological treatment, but the underlying mechanisms are mostly unknown. We performed a genome-wide association study of metabolic and cardiovascular risk factors during pharmacological therapy. Twelve indicators of metabolic side effects as well as cardiovascular risk factors were analyzed in a naturalistic sample of 594 patients of Norwegian ancestry. We analyzed interactions between gene variants and three categories of psychopharmacological agents based on their reported potential for side effects. For body mass index (BMI), two significantly associated loci were identified on 8q21.3. There were seven markers in one 30-kb region, and the strongest signal was rs7838490. In another locus 140kb away, six markers were significant, and rs6989402 obtained the strongest signal. Both of these loci are located upstream of the gene matrix metalloproteinase 16 (MMP16). For high density lipoprotein cholesterol (HDL-C), marker rs11615274 on 12q21 was significant. The results highlight three genomic regions potentially harboring susceptibility genes for drug-induced metabolic side effects, identifying MMP16 as a candidate gene. This deserves to be replicated in additional populations to provide more evidence for molecular genetic mechanisms of side effects during psychopharmacological treatment.

283 European ancestry schizophrenia cases, 213 European ancestry bipolar disorder cases, 98 European ancestry psychosis cases