Genome-wide gene-environment interactions in neuroticism: an exploratory study across 25 environments

Josefin Werme; Sophie van der Sluis; Danielle Posthuma; Christiaan A. de Leeuw

doi:10.1038/s41398-021-01288-9

Genome-wide gene-environment interactions in neuroticism: an exploratory study across 25 environments

Josefin Werme^*, Sophie van der Sluis, Danielle Posthuma, Christiaan A. de Leeuw

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Article number	180
Journal	Translational Psychiatry
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41398-021-01288-9
Publication status	Published - Jun 2021

Bibliographical note

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.

Access to Document

10.1038/s41398-021-01288-9

Persistent URL (handle)

Copy link address

Cite this

@article{025a37737d5c4123964d506d0b0cdc09,

title = "Genome-wide gene-environment interactions in neuroticism: an exploratory study across 25 environments",

abstract = "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.",

author = "Josefin Werme and {van der Sluis}, Sophie and Danielle Posthuma and {de Leeuw}, {Christiaan A.}",

note = "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: {\textcopyright} 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

year = "2021",

month = jun,

doi = "10.1038/s41398-021-01288-9",

language = "English",

volume = "11",

journal = "Translational Psychiatry",

issn = "2158-3188",

publisher = "Nature Publishing Group",

number = "1",

}

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

Y1 - 2021/6

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.

UR - http://www.scopus.com/inward/record.url?scp=85103209737&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85103209737&partnerID=8YFLogxK

U2 - 10.1038/s41398-021-01288-9

DO - 10.1038/s41398-021-01288-9

M3 - Article

C2 - 33753719

AN - SCOPUS:85103209737

SN - 2158-3188

VL - 11

JO - Translational Psychiatry

JF - Translational Psychiatry

IS - 1

M1 - 180

ER -

Genome-wide gene-environment interactions in neuroticism: an exploratory study across 25 environments

Abstract

Bibliographical note

Access to Document

Persistent URL (handle)

Other files and links

Fingerprint

Cite this