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Nat Commun. 2018 Apr 16;9(1):1470. doi: 10.1038/s41467-018-03819-3.

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

Author information

1
Division of Psychiatry, University of Edinburgh, Edinburgh, EH10 5HF, UK. D.Howard@ed.ac.uk.
2
Division of Psychiatry, University of Edinburgh, Edinburgh, EH10 5HF, UK.
3
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
4
Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
5
Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, SE5 8AF, UK.
6
NIHR Biomedical Research Centre for Mental Health, South London and Maudsley NHS Trust, London, SE5 8AF, UK.
7
Institute of Health and Wellbeing, University of Glasgow, Glasgow, G12 8RZ, UK.
8
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, 171 77, Sweden.
9
Department of Genetics, University of North Carolina, Chapel Hill, 27599, NC, USA.
10
Department of Psychiatry, University of North Carolina, Chapel Hill, 27599, NC, USA.
11
Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.

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.

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