Abstract

Depression is a polygenic trait that causes extensive periods of disability. Previous genetic studies have identified common risk variants which have progressively increased in number with increasing sample sizes of the respective studies. Here, we conduct a genome-wide association study in 322,580 UK Biobank participants for three depression-related phenotypes: broad depression, probable major depressive disorder (MDD), and International Classification of Diseases (ICD, version 9 or 10)-coded MDD. We identify 17 independent loci that are significantly associated (P < 5 × 10−8) across the three phenotypes. The direction of effect of these loci is consistently replicated in an independent sample, with 14 loci likely representing novel findings. Gene sets are enriched in excitatory neurotransmission, mechanosensory behaviour, post synapse, neuron spine and dendrite functions. Our findings suggest that broad depression is the most tractable UK Biobank phenotype for discovering genes and gene sets that further our understanding of the biological pathways underlying depression.

Details

Title
Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways
Author
Howard, David M 1   VIAFID ORCID Logo  ; Adams, Mark J 1   VIAFID ORCID Logo  ; Shirali, Masoud 1   VIAFID ORCID Logo  ; Toni-Kim, Clarke 1 ; Marioni, Riccardo E 2 ; Davies, Gail 3 ; Coleman, Jonathan R I 4   VIAFID ORCID Logo  ; Alloza, Clara 1 ; Shen, Xueyi 1   VIAFID ORCID Logo  ; Barbu, Miruna C 1 ; Wigmore, Eleanor M 1 ; Gibson, Jude 1 ; Agee, Michelle 5 ; Alipanahi, Babak 5 ; Auton, Adam 5 ; Bell, Robert K 5 ; Bryc, Katarzyna 5 ; Elson, Sarah L 5 ; Fontanillas, Pierre 5 ; Furlotte, Nicholas A 5 ; Hinds, David A 5 ; Huber, Karen E 5 ; Kleinman, Aaron 5 ; Litterman, Nadia K 5 ; McCreight, Jennifer C 5 ; McIntyre, Matthew H 5 ; Mountain, Joanna L 5 ; Noblin, Elizabeth S 5 ; Northover, Carrie A M 5 ; Pitts, Steven J 5 ; Sathirapongsasuti, J Fah 5 ; Sazonova, Olga V 5 ; Shelton, Janie F 5 ; Shringarpure, Suyash 5 ; Tian, Chao 5 ; Tung, Joyce Y 5 ; Vacic, Vladimir 5 ; Wilson, Catherine H 5 ; Hagenaars, Saskia P 4 ; Lewis, Cathryn M 4   VIAFID ORCID Logo  ; Ward, Joey 6 ; Smith, Daniel J 6   VIAFID ORCID Logo  ; Sullivan, Patrick F 7 ; Haley, Chris S 8   VIAFID ORCID Logo  ; Breen, Gerome 4 ; Deary, Ian J 3 ; McIntosh, Andrew M 9   VIAFID ORCID Logo 

1  Division of Psychiatry, University of Edinburgh, Edinburgh, UK 
2  Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK 
3  Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Department of Psychology, University of Edinburgh, Edinburgh, UK 
4  Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK; NIHR Biomedical Research Centre for Mental Health, South London and Maudsley NHS Trust, London, UK 
5  23andMe, Inc., Mountain View, CA, USA 
6  Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK 
7  Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA; Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA 
8  Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK 
9  Division of Psychiatry, University of Edinburgh, Edinburgh, UK; Department of Psychology, University of Edinburgh, Edinburgh, UK 
Pages
1-10
Publication year
2018
Publication date
Apr 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-03819-3
ProQuest document ID
2025801084
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.