A new genetic locus for antipsychotic-induced weight gain: A genome-wide study of first-episode psychosis patients using amisulpride (from the OPTiMiSE cohort)

Sophie E. ter Hark, Stephane Jamain, Dick Schijven, Bochao D. Lin, Mark K. Bakker, Anne Boland-Auge, Jean-Francois Deleuze, Rejane Troudet, Anil K. Malhotra, Sinan Guloksuz, Christiaan H. Vinkers, Bjorn H. Ebdrup, Rene S. Kahn, Marion Leboyer, Jurjen J. Luykx*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Web of Science)

Abstract

Background:

Antipsychotic-induced weight gain is a common and debilitating side effect of antipsychotics. Although genome-wide association studies of antipsychotic-induced weight gain have been performed, few genome-wide loci have been discovered. Moreover, these genome-wide association studies have included a wide variety of antipsychotic compounds.

Aims:

We aim to gain more insight in the genomic loci affecting antipsychotic-induced weight gain. Given the variable pharmacological properties of antipsychotics, we hypothesized that targeting a single antipsychotic compound would provide new clues about genomic loci affecting antipsychotic-induced weight gain.

Methods:

All subjects included for this genome-wide association study (n=339) were first-episode schizophrenia spectrum disorder patients treated with amisulpride and were minimally medicated (defined as antipsychotic use

Results:

Our genome-wide association analyses for antipsychotic-induced weight gain yielded one genome-wide significant hit (rs78310016; beta=1.05; p=3.66 x 10(-08); n=206) in a locus not previously associated with antipsychotic-induced weight gain or body mass index. Minor allele carriers had an odds ratio of 3.98 (p=1.0 x 10(-03)) for clinically meaningful antipsychotic-induced weight gain (> 7% of baseline weight). In silico analysis elucidated a chromatin interaction with 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1. In an attempt to replicate single-nucleotide polymorphisms previously associated with antipsychotic-induced weight gain, we found none were associated with amisulpride-induced weight gain.

Conclusion:

Our findings suggest the involvement of rs78310016 and possibly 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1 in antipsychotic-induced weight gain. In line with the unique binding profile of this atypical antipsychotic, our findings furthermore hint that biological mechanisms underlying amisulpride-induced weight gain differ from antipsychotic-induced weight gain by other atypical antipsychotics.

Original languageEnglish
Article number0269881120907972
Pages (from-to)524-531
Number of pages8
JournalJournal of Psychopharmacology
Volume34
Issue number5
DOIs
Publication statusPublished - May 2020

Keywords

  • Pharmacogenetics
  • antipsychotics
  • body mass index
  • amisulpride-induced weight gain
  • schizophrenia
  • GWAS
  • SELENOPROTEIN-P
  • GROWTH-HORMONE
  • SCHIZOPHRENIA
  • ASSOCIATION
  • INSULIN
  • MEDICATIONS
  • CLOZAPINE
  • VARIANTS
  • PROFILES
  • SEPP1

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