TY - JOUR
T1 - Genome-wide gene-environment interactions in neuroticism
T2 - an exploratory study across 25 environments
AU - Werme, Josefin
AU - van der Sluis, Sophie
AU - Posthuma, Danielle
AU - de Leeuw, Christiaan A.
N1 - Funding Information: This work was funded by COSYN (Comorbidity and Synapse Biology in Clinically Overlapping Psychiatric Disorders: Horizon 2020 Program of the European Union under RIA grant agreement 667301 to D.P.) and the Netherlands Organization for Scientific Research (NWO: VICI 435-14-005). The analyses were carried out on the Genetic Cluster Computer, which is financed by the Netherlands Organization for Scientific Research (NWO: 480-05-003), by the VU University (Amsterdam, The Netherlands) and the Dutch Brain Foundation, hosted by the Dutch National Computing and Networking Services SurfSARA. This research was conducted using the UK Biobank Resource (application number 16406), and we would like to thank all participants who consented to participate in this research, as well as the researchers involved in the collection of the data. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - Gene-environment interactions (GxE) are often suggested to play an important role in the aetiology of psychiatric phenotypes, yet so far, only a handful of genome-wide environment interaction studies (GWEIS) of psychiatric phenotypes have been conducted. Representing the most comprehensive effort of its kind to date, we used data from the UK Biobank to perform a series of GWEIS for neuroticism across 25 broadly conceptualised environmental risk factors (trauma, social support, drug use, physical health). We investigated interactions on the level of SNPs, genes, and gene-sets, and computed interaction-based polygenic risk scores (PRS) to predict neuroticism in an independent sample subset (N = 10,000). We found that the predictive ability of the interaction-based PRSs did not significantly improve beyond that of a traditional PRS based on SNP main effects from GWAS, but detected one variant and two gene-sets showing significant interaction signal after correction for the number of analysed environments. This study illustrates the possibilities and limitations of a comprehensive GWEIS in currently available sample sizes.
AB - Gene-environment interactions (GxE) are often suggested to play an important role in the aetiology of psychiatric phenotypes, yet so far, only a handful of genome-wide environment interaction studies (GWEIS) of psychiatric phenotypes have been conducted. Representing the most comprehensive effort of its kind to date, we used data from the UK Biobank to perform a series of GWEIS for neuroticism across 25 broadly conceptualised environmental risk factors (trauma, social support, drug use, physical health). We investigated interactions on the level of SNPs, genes, and gene-sets, and computed interaction-based polygenic risk scores (PRS) to predict neuroticism in an independent sample subset (N = 10,000). We found that the predictive ability of the interaction-based PRSs did not significantly improve beyond that of a traditional PRS based on SNP main effects from GWAS, but detected one variant and two gene-sets showing significant interaction signal after correction for the number of analysed environments. This study illustrates the possibilities and limitations of a comprehensive GWEIS in currently available sample sizes.
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U2 - https://doi.org/10.1038/s41398-021-01288-9
DO - https://doi.org/10.1038/s41398-021-01288-9
M3 - Article
C2 - 33753719
SN - 2158-3188
VL - 11
JO - Translational Psychiatry
JF - Translational Psychiatry
IS - 1
M1 - 180
ER -