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

Ter Hark, S. E., Jamain, S., Schijven, D., Lin, B. D., Bakker, M. K., Boland-Auge, A., et al. (2020). A new genetic locus for antipsychotic-induced weight gain: A genome-wide study of first-episode psychosis patients using amisulpride (from the OPTiMiSE cohort). Journal of Psychopharmacology, 34(5), 524-531. doi:10.1177/0269881120907972.

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0269881120907972-1.pdf (Publisher version), 425KB
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 Creators:
Ter Hark, Sophie E, Author
Jamain, Stephane, Author
Schijven, Dick1, Author           
Lin, Bochao D, Author
Bakker, Mark K, Author
Boland-Auge, Anne, Author
Deleuze, Jean-François, Author
Troudet, Réjane, Author
Malhotra, Anil K, Author
Gülöksüz, Sinan, Author
Vinkers, Christiaan H, Author
Ebdrup, Bjørn H, Author
Kahn, René S, Author
Leboyer, Marion, Author
Luykx, Jurjen J, Author
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1Utrecht University, Utrecht, The Netherlands, ou_persistent22              

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 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 <2?weeks in the previous year and/or <6?weeks lifetime). Weight gain was defined as the increase in body mass index from before until approximately 1 month after amisulpride treatment.Results:Our genome-wide association analyses for antipsychotic-induced weight gain yielded one genome-wide significant hit (rs78310016; ?=1.05; p=3.66 ? 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 ? 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.

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Language(s): eng - English
 Dates: 2020-03-042020-03
 Publication Status: Issued
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1177/0269881120907972
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Title: Journal of Psychopharmacology
  Other : J. Psychopharmacol.
Source Genre: Journal
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Publ. Info: Oxford, UK : Sage Publications, Inc.
Pages: - Volume / Issue: 34 (5) Sequence Number: - Start / End Page: 524 - 531 Identifier: ISSN: 0269-8811
CoNE: https://pure.mpg.de/cone/journals/resource/954925501173