A mega-analysis of genome-wide association studies for major depressive disorder

Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium, Wray, Naomi, Byrne, Enda M., Martin, Nicholas G., Gordon, Scott D., Henders, Anjali K., Montgomery, Grant M. and Nyholt, Dale R. (2013) A mega-analysis of genome-wide association studies for major depressive disorder. Molecular Psychiatry, 18 4: 497-511. doi:10.1038/mp.2012.21

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Author Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium
Wray, Naomi
Byrne, Enda M.
Martin, Nicholas G.
Gordon, Scott D.
Henders, Anjali K.
Montgomery, Grant M.
Nyholt, Dale R.
Total Author Count Override 116
Title A mega-analysis of genome-wide association studies for major depressive disorder
Journal name Molecular Psychiatry   Check publisher's open access policy
ISSN 1359-4184
Publication date 2013-04
Year available 2012
Sub-type Article (original research)
DOI 10.1038/mp.2012.21
Open Access Status File (Author Post-print)
Volume 18
Issue 4
Start page 497
End page 511
Total pages 15
Place of publication London, United Kingdom
Publisher Nature
Collection year 2013
Language eng
Formatted abstract
Prior genome-wide association studies (GWAS) of major depressive disorder (MDD) have met with limited success. We sought to increase statistical power to detect disease loci by conducting a GWAS mega-analysis for MDD. In the MDD discovery phase, we analyzed more than 1.2 million autosomal and X chromosome single-nucleotide polymorphisms (SNPs) in 18 759 independent and unrelated subjects of recent European ancestry (9240 MDD cases and 9519 controls). In the MDD replication phase, we evaluated 554 SNPs in independent samples (6783 MDD cases and 50 695 controls). We also conducted a cross-disorder meta-analysis using 819 autosomal SNPs with P<0.0001 for either MDD or the Psychiatric GWAS Consortium bipolar disorder (BIP) mega-analysis (9238 MDD cases/8039 controls and 6998 BIP cases/7775 controls). No SNPs achieved genome-wide significance in the MDD discovery phase, the MDD replication phase or in pre-planned secondary analyses (by sex, recurrent MDD, recurrent early-onset MDD, age of onset, pre-pubertal onset MDD or typical-like MDD from a latent class analyses of the MDD criteria). In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5 × 10 -8), and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083-53 822 102, minimum P=5.9 × 10 -9 at rs2535629). Although this is the largest genome-wide analysis of MDD yet conducted, its high prevalence means that the sample is still underpowered to detect genetic effects typical for complex traits. Therefore, we were unable to identify robust and replicable findings. We discuss what this means for genetic research for MDD. The 3p21.1 MDD-BIP finding should be interpreted with caution as the most significant SNP did not replicate in MDD samples, and genotyping in independent samples will be needed to resolve its status.
Keyword Genetics
Genome-wide association study
Major depressive disorder
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Advance online publication: 3 April 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2013 Collection
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Citation counts: TR Web of Science Citation Count  Cited 78 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 280 times in Scopus Article | Citations
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Created: Mon, 05 Nov 2012, 15:29:53 EST by Debra McMurtrie on behalf of Queensland Brain Institute