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 language | English |
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Article number | 0269881120907972 |
Pages (from-to) | 524-531 |
Number of pages | 8 |
Journal | Journal of Psychopharmacology |
Volume | 34 |
Issue number | 5 |
DOIs | |
Publication status | Published - 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