4 new genetic variants associated with weight gain

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 (Image: Pixabay CC0)
(Image: Pixabay CC0)

A research group at the University of Lausanne has carried out the largest genome-wide study of weight gain induced by psychotropic drugs. This work has identified 4 new genetic variants associated with this metabolic disorder.

Interindividual variability in psychotropic drug-induced weight gain

The prevalence of metabolic disorders in the psychiatric population is a cause for concern, and particularly high among patients taking psychotropic drugs that induce weight gain. While some may rapidly become obese or overweight after starting pharmacological treatment, others seem to be protected. This significant inter-individual variability represents a major challenge for physicians and their patients, not least because undesirable metabolic effects are a major source of treatment interruption, associated with an increased risk of relapse.

Over the past few years, Prof. Chin Bin Eap’s research group (FBM and Centre de neurosciences psychiatriques (CNP) at CHUV) has demonstrated that numerous clinical, genetic and environmental factors are involved in psychotropic drug-induced weight gain and metabolic worsening. Identifying these factors is essential for the clinical follow-up of psychiatric patients, as it enables us to focus on those at highest risk of developing metabolic disorders, and can help clinicians to propose appropriate psychotropic treatment.

Identification of four new genetic factors

To our knowledge, this research represents the largest genome-wide association study (GWAS) to date on the evolution of body mass index (BMI) during psychotropic treatment. More specifically, genetic variants from the entire human genome were analyzed for association with changes in BMI during the first six months of metabolic-inducing psychotropic treatment (including antipsychotics, mood stabilizers and certain antidepressants), in 1135 patients from the PsyMetab cohort.

Four genetic variants were associated with an increase in BMI at a genome-wide significant level (p<5x10-8). In particular, rs7736552 (near the MAN2A1 gene), rs11074029 (in the SLCO3A1 gene), rs117496040 (near the DEFB1 gene) and rs7647863 (in the IQSEC1 gene) were associated with BMI slope or variation during psychotropic treatment.

These findings provide new information on the risk of developing psychotropic drug-induced metabolic side effects. However, these results need to be confirmed in independent cohorts, before they can potentially be considered in clinical practice.

This study was carried out in collaboration with several departments of the Department of Psychiatry (Prof. Philippe Conus, General Psychiatry Department; Prof. Armin von Gunten, University Department of Advanced Age Psychiatry, and Prof. Kerstin von Plessen, University Department of Child and Adolescent Psychiatry), with Prof. Zoltán Kutalik of the University of Lausanne, and with other centers.