Format

Send to

Choose Destination
Nat Neurosci. 2019 Feb 4. doi: 10.1038/s41593-018-0326-7. [Epub ahead of print]

Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions.

Author information

1
Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK. D.Howard@ed.ac.uk.
2
Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.
3
Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
4
NIHR Biomedical Research Centre for Mental Health, South London and Maudsley NHS Trust, London, UK.
5
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
6
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
7
Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
8
Department of Psychology, University of Edinburgh, Edinburgh, UK.
9
Medical Research Council (MRC) Integrative Epidemiology Unit, Population Health, Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
10
Institute of Epidemiology & Social Medicine, University of Münster, Münster, Germany.
11
Department of Psychiatry, University of Münster, Münster, Germany.
12
Department of Psychiatry, University of Melbourne, Victoria, Australia.
13
Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
14
23andMe, Inc, Mountain View, CA, USA.
15
Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
16
Department of Psychiatry, Charite Universitatsmedizin Berlin Campus Benjamin Franklin, Berlin, Germany.
17
Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
18
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
19
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
20
Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
21
Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA.

Abstract

Major depression is a debilitating psychiatric illness that is typically associated with low mood and anhedonia. Depression has a heritable component that has remained difficult to elucidate with current sample sizes due to the polygenic nature of the disorder. To maximize sample size, we meta-analyzed data on 807,553 individuals (246,363 cases and 561,190 controls) from the three largest genome-wide association studies of depression. We identified 102 independent variants, 269 genes, and 15 genesets associated with depression, including both genes and gene pathways associated with synaptic structure and neurotransmission. An enrichment analysis provided further evidence of the importance of prefrontal brain regions. In an independent replication sample of 1,306,354 individuals (414,055 cases and 892,299 controls), 87 of the 102 associated variants were significant after multiple testing correction. These findings advance our understanding of the complex genetic architecture of depression and provide several future avenues for understanding etiology and developing new treatment approaches.

PMID:
30718901
DOI:
10.1038/s41593-018-0326-7

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center