Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned

N R Wray; M L Pergadia; D H R Blackwood; B W J H Penninx; S D Gordon; D R Nyholt; S Ripke; D J MacIntyre; K A McGhee; A W Maclean; J H Smit; J J Hottenga; G Willemsen; C M Middeldorp; E J C de Geus; C M Lewis; P McGuffin; I B Hickie; E J C G van den Oord; J Z Liu; S Macgregor; B P McEvoy; E M Byrne; S E Medland; Dixie J Statham; A K Henders; A C Heath; G W Montgomery; N G Martin; D I Boomsma; P A F Madden; P F Sullivan

doi:10.1038/mp.2010.109

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Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned

Journal article

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Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned

N R Wray, M L Pergadia, D H R Blackwood, B W J H Penninx, S D Gordon, D R Nyholt, S Ripke, D J MacIntyre, K A McGhee, A W Maclean, …

Molecular Psychiatry, Vol.17, pp.36-48

2012

DOI: https://doi.org/10.1038/mp.2010.109

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Abstract

major depressive disorder

depression

genome-wide association study

CACBA1C

ADCY3

GAL

Major depressive disorder (MDD) is a common complex disorder with a partly genetic etiology. We conducted a genome-wide association study of the MDD2000+ sample (2431 cases, 3673 screened controls and >1 M imputed single-nucleotide polymorphisms (SNPs)). No SNPs achieved genome-wide significance either in the MDD2000+ study, or in meta-analysis with two other studies totaling 5763 cases and 6901 controls. These results imply that common variants of intermediate or large effect do not have main effects in the genetic architecture of MDD. Suggestive but notable results were (a) gene-based tests suggesting roles for adenylate cyclase 3 (ADCY3, 2p23.3) and galanin (GAL, 11q13.3); published functional evidence relates both of these to MDD and serotonergic signaling; (b) support for the bipolar disorder risk variant SNP rs1006737 in CACNA1C (P=0.020, odds ratio=1.10); and (c) lack of support for rs2251219, a SNP identified in a meta-analysis of affective disorder studies (P=0.51). We estimate that sample sizes 1.8- to 2.4-fold greater are needed for association studies of MDD compared with those for schizophrenia to detect variants that explain the same proportion of total variance in liability. Larger study cohorts characterized for genetic and environmental risk factors accumulated prospectively are likely to be needed to dissect more fully the etiology of MDD.

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Title: Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned
Authors: N R Wray (Author) - Queensland Institute of Medical Research
M L Pergadia (Author) - Washington University School of Medicine, United States
D H R Blackwood (Author) - University of Edinburgh, United Kingdom
B W J H Penninx (Author) - VU University Amsterdam, Netherlands
S D Gordon (Author) - Queensland Institute of Medical Research
D R Nyholt (Author) - Queensland Institute of Medical Research
S Ripke (Author) - Massachusetts General Hospital, United States
D J MacIntyre (Author) - University of Edinburgh, United Kingdom
K A McGhee (Author) - University of Edinburgh, United Kingdom
A W Maclean (Author) - University of Edinburgh, United Kingdom
J H Smit (Author) - VU University Amsterdam, Netherlands
J J Hottenga (Author) - VU University Amsterdam, Netherlands
G Willemsen (Author) - VU University Amsterdam, Netherlands
C M Middeldorp (Author) - VU University Amsterdam, Netherlands
E J C de Geus (Author) - VU University Amsterdam, Netherlands
C M Lewis (Author) - King's College London, United Kingdom
P McGuffin (Author) - King's College London, United Kingdom
I B Hickie (Author) - University of Sydney
E J C G van den Oord (Author) - Virginia Commonwealth University, United States
J Z Liu (Author)
S Macgregor (Author) - Queensland Institute of Medical Research
B P McEvoy (Author) - Queensland Institute of Medical Research
E M Byrne (Author) - Queensland Institute of Medical Research
S E Medland (Author) - Queensland Institute of Medical Research
Dixie J Statham (Author) - University of the Sunshine Coast - Faculty of Arts and Business
A K Henders (Author) - Queensland Institute of Medical Research
A C Heath (Author) - Washington University School of Medicine, United States
G W Montgomery (Author) - Queensland Institute of Medical Research
N G Martin (Author) - Queensland Institute of Medical Research
D I Boomsma (Author) - VU University Amsterdam, Netherlands
P A F Madden (Author) - Washington University School of Medicine, United States
P F Sullivan (Author) - University of North Carolina, United States
Publication details: Molecular Psychiatry, Vol.17, pp.36-48
Publisher: Nature Publishing Group
Date published: 2012
DOI: 10.1038/mp.2010.109
ISSN: 1359-4184
Organisation Unit: School of Social Sciences - Legacy; University of the Sunshine Coast, Queensland
Language: English
Record Identifier: 99450252802621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Biochemistry & Molecular Biology; Neurosciences; Psychiatry

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