Weight gain induced by psychotropic drugs: 4 genetic variants identified

2023-05-30 10:09:27

The research group of Prof. Chin Bin Eap (Department of Psychiatry, CHUV-UNIL) published an article on May 12, 2023 in the prestigious scientific journal Molecular Psychiatry. This is the largest genome-wide study of psychotropic drug-induced weight gain. It identified 4 new genetic variants associated with this metabolic disorder. Here is the abstract of this article.

Patients with mental disorders are at high risk of developing cardiovascular disease, resulting in reduced life expectancy. Genetic variants may display a greater influence on cardiometabolic characteristics in psychiatric cohorts compared to the general population. The difference may be due to a complex interaction between the mental disorder or the drugs used to treat it and metabolic regulations. Previous genome-wide association studies (GWAS) of antipsychotic-induced weight gain included small numbers of participants and/or were limited to patients taking a specific antipsychotic. We conducted a GWAS of changes in body mass index (BMI) during the first (i.e., ≤ 6) months of treatment with psychotropic drugs that induce metabolic disorders (i.e., i.e. antipsychotics, mood stabilizers and some antidepressants) in 1135 patients from the PsyMetab cohort. Six highly correlated BMI phenotypes (i.e., BMI change and BMI slope after distinct durations of psychotropic treatment) were considered in the analyses. Our results showed that four novel loci (precise locations of a gene on a chromosome) were associated with altered BMI during genome-wide processing (p < 5 × 10 −8 ): rs7736552 (near by MAN2A1 ), rs11074029 (in SLCO3A1 ), rs117496040 (near DEFB1 ) and rs7647863 (in IQSEC1).

Associations between the four loci and alternative BMI-altering phenotypes showed consistent effects. Replication analyzes in 1622 UK Biobank participants on psychotropic therapy showed a consistent association between rs7736552 and BMI slope ( p= 0,017).

These results provide new insights into the metabolic side effects induced by psychotropic drugs and underscore the need for future studies to replicate these associations in larger cohorts..

• Identification of four new loci associated with weight gain induced by psychotropic drugs in a Swiss longitudinal psychiatric study: a GWAS analysis, Jennifer Sjaarda, Aurélie Delacrétaz, Céline Dubath, Nermine Laaboub, Marianna Piras, Claire Grosu, Frederik Vandenberghe, Séverine Crettol , Nicolas Ansermot , Franziska Gamma , Kerstin Jessica Plessen , Armin von Gunten , Philippe Conus , Zoltan Kutalik & Chin B.Eap, Molecular Psychiatry, May 12, 2023.

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