Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways

Howard, D. M. et al. (2018) Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways. Nature Communications, 9, 1470. (doi: 10.1038/s41467-018-03819-3) (PMID:29662059) (PMCID:PMC5902628)

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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.

Item Type:Articles
Additional Information:We are grateful to the research participants and employees of UK Biobank and 23andMe. A.M.McI, and I.J.D. acknowledge support from the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” (STRADL) Reference 104036/Z/14/Z and the Sackler Foundation. I.J.D. is supported by the Centre for Cognitive Ageing and Cognitive Epidemiology, which is funded by the Medical Research Council and the Biotechnology and Biological Sciences Research Council (MR/K026992/1). This investigation represents independent research part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London.
Glasgow Author(s) Enlighten ID:Smith, Professor Daniel and Ward, Dr Joey
Authors: Howard, D. M., Adams, M. J., Shirali, M., Clarke, T.-K., Marioni, R. E., Davies, G., Coleman, J. R. I., Alloza, C., Shen, X., Barbu, M. C., Wigmore, E. M., Gibson, J., Hagenaars, S., Lewis, C. M., Ward, J., Smith, D. J., Sullivan, P. F., Haley, C. S., Breen, G., Deary, I. J., and McIntosh, A. M.
College/School:College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
Journal Name:Nature Communications
Publisher:Nature Publishing Group
ISSN (Online):2041-1723
Published Online:16 April 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Nature Communications 9:1470
Publisher Policy:Reproduced under a Creative Commons License
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