Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Genome-wide meta-analyses of stratified depression in Generation Scotland and UK Biobank

View ORCID ProfileLynsey S. Hall, View ORCID ProfileMark J. Adams, Aleix Arnau-Soler, View ORCID ProfileToni-Kim Clarke, View ORCID ProfileDavid M. Howard, View ORCID ProfileYanni Zeng, View ORCID ProfileGail Davies, Saskia P. Hagenaars, Ana Maria Fernandez-Pujals, Jude Gibson, View ORCID ProfileEleanor M. Wigmore, Thibaud S. Boutin, Caroline Hayward, Generation Scotland, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, View ORCID ProfileDavid J. Porteous, View ORCID ProfileIan J. Deary, View ORCID ProfilePippa A. Thomson, Chris S. Haley, View ORCID ProfileAndrew M. McIntosh
doi: https://doi.org/10.1101/130229
Lynsey S. Hall
1Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh UK
2Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Lynsey S. Hall
Mark J. Adams
1Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Mark J. Adams
Aleix Arnau-Soler
3Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Toni-Kim Clarke
1Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Toni-Kim Clarke
David M. Howard
1Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for David M. Howard
Yanni Zeng
1Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh UK
4Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Yanni Zeng
Gail Davies
5Department of Psychology, University of Edinburgh, Edinburgh, UK
6Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Gail Davies
Saskia P. Hagenaars
1Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh UK
5Department of Psychology, University of Edinburgh, Edinburgh, UK
6Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ana Maria Fernandez-Pujals
1Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jude Gibson
1Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eleanor M. Wigmore
1Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Eleanor M. Wigmore
Thibaud S. Boutin
4Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Caroline Hayward
4Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Generation Scotland
7A collaboration between the University Medical Schools and National Health Service in Aberdeen, Dundee, Edinburgh and Glasgow, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
8For a full list of MDD working group of the PGC investigators, see the Supplementary Material
David J. Porteous
3Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for David J. Porteous
Ian J. Deary
5Department of Psychology, University of Edinburgh, Edinburgh, UK
6Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ian J. Deary
Pippa A. Thomson
3Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
6Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Pippa A. Thomson
Chris S. Haley
4Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew M. McIntosh
1Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh UK
6Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Andrew M. McIntosh
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Few replicable genetic associations for Major Depressive Disorder (MDD) have been identified. However recent studies of depression have identified common risk variants by using either a broader phenotype definition in very large samples, or by reducing the phenotypic and ancestral heterogeneity of MDD cases. Here, a range of genetic analyses were applied to data from two large British cohorts, Generation Scotland and UK Biobank, to ascertain whether it is more informative to maximize the sample size by using data from all available cases and controls, or to use a refined subset of the data - stratifying by MDD recurrence or sex. Meta-analysis of GWAS data in males from these two studies yielded one genome-wide significant locus on 3p22.3. Three associated genes within this region (CRTAP, GLB1, and TMPPE) were significantly associated in subsequent gene-based tests. Meta-analyzed MDD, recurrent MDD and female MDD were each genetically correlated with 6 of 200 health-correlated traits, namely neuroticism, depressive symptoms, subjective well-being, MDD, a cross-disorder phenotype and Bipolar Disorder. Meta-analyzed male MDD showed no statistically significant correlations with these traits after correction for multiple testing. Whilst stratified GWAS analysis revealed a genome-wide significant locus for male MDD, the lack of independent replication, the equivalent SNP-based heritability estimates and the consistent pattern of genetic correlation with other health-related traits suggests that phenotypic stratification in currently available sample sizes is currently weakly justified. Based upon existing studies and our findings, the strategy of maximizing sample sizes is likely to provide the greater gain.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted April 24, 2017.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Genome-wide meta-analyses of stratified depression in Generation Scotland and UK Biobank
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Genome-wide meta-analyses of stratified depression in Generation Scotland and UK Biobank
Lynsey S. Hall, Mark J. Adams, Aleix Arnau-Soler, Toni-Kim Clarke, David M. Howard, Yanni Zeng, Gail Davies, Saskia P. Hagenaars, Ana Maria Fernandez-Pujals, Jude Gibson, Eleanor M. Wigmore, Thibaud S. Boutin, Caroline Hayward, Generation Scotland, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, David J. Porteous, Ian J. Deary, Pippa A. Thomson, Chris S. Haley, Andrew M. McIntosh
bioRxiv 130229; doi: https://doi.org/10.1101/130229
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Genome-wide meta-analyses of stratified depression in Generation Scotland and UK Biobank
Lynsey S. Hall, Mark J. Adams, Aleix Arnau-Soler, Toni-Kim Clarke, David M. Howard, Yanni Zeng, Gail Davies, Saskia P. Hagenaars, Ana Maria Fernandez-Pujals, Jude Gibson, Eleanor M. Wigmore, Thibaud S. Boutin, Caroline Hayward, Generation Scotland, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, David J. Porteous, Ian J. Deary, Pippa A. Thomson, Chris S. Haley, Andrew M. McIntosh
bioRxiv 130229; doi: https://doi.org/10.1101/130229

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genetics
Subject Areas
All Articles
  • Animal Behavior and Cognition (2427)
  • Biochemistry (4784)
  • Bioengineering (3328)
  • Bioinformatics (14656)
  • Biophysics (6629)
  • Cancer Biology (5162)
  • Cell Biology (7417)
  • Clinical Trials (138)
  • Developmental Biology (4355)
  • Ecology (6869)
  • Epidemiology (2057)
  • Evolutionary Biology (9903)
  • Genetics (7338)
  • Genomics (9509)
  • Immunology (4545)
  • Microbiology (12657)
  • Molecular Biology (4936)
  • Neuroscience (28280)
  • Paleontology (199)
  • Pathology (804)
  • Pharmacology and Toxicology (1388)
  • Physiology (2019)
  • Plant Biology (4487)
  • Scientific Communication and Education (976)
  • Synthetic Biology (1297)
  • Systems Biology (3909)
  • Zoology (725)