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

Molecular psychiatry, 2013-04, Vol.18 (4), p.497-511 [Peer Reviewed Journal]

2015 INIST-CNRS ;COPYRIGHT 2013 Nature Publishing Group ;Copyright Nature Publishing Group Apr 2013 ;Macmillan Publishers Limited 2013. ;2013 Macmillan Publishers Limited All rights reserved 2013 ;ISSN: 1359-4184 ;ISSN: 1476-5578 ;EISSN: 1476-5578 ;DOI: 10.1038/mp.2012.21 ;PMID: 22472876

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Title:
A mega-analysis of genome-wide association studies for major depressive disorder
Author: Ripke, Stephan ; Wray, Naomi R ; Lewis, Cathryn M ; Hamilton, Steven P ; Weissman, Myrna M ; Breen, Gerome ; Byrne, Enda M ; Blackwood, Douglas H R ; Boomsma, Dorret I ; Cichon, Sven ; Heath, Andrew C ; Holsboer, Florian ; Lucae, Susanne ; Madden, Pamela A F ; Martin, Nicholas G ; McGuffin, Peter ; Muglia, Pierandrea ; Noethen, Markus M ; Penninx, Brenda P ; Potash, James B ; Rietschel, Marcella ; Lin, Danyu ; Müller-Myhsok, Bertram ; Shi, Jianxin ; Steinberg, Stacy ; Grabe, Hans J ; Lichtenstein, Paul ; Magnusson, Patrik ; Perlis, Roy H ; Preisig, Martin ; Smoller, Jordan W ; Stefansson, Kari ; Kutalik, Zoltan ; Teumer, Alexander ; Viktorin, Alexander ; Barnes, Michael R ; Bettecken, Thomas ; Binder, Elisabeth B ; Castro, Victor M ; Churchill, Susanne E ; Coryell, William H ; Craddock, Nick ; Craig, Ian W ; Czamara, Darina ; De Geus, Eco J ; Degenhardt, Franziska ; Farmer, Anne E ; Gallagher, Patience J ; Gordon, Scott D ; Goryachev, Sergey ; Gross, Magdalena ; Henders, Anjali K ; Herms, Stefan ; Hickie, Ian B ; Hoefels, Susanne ; Hoogendijk, Witte ; Iosifescu, Dan V ; Ising, Marcus ; Jones, Ian ; Jones, Lisa ; Jung-Ying, Tzeng ; Knowles, James A ; Kohli, Martin A ; Korszun, Ania ; Landen, Mikael ; Lawson, William B ; Lewis, Glyn ; Macintyre, Donald ; Maier, Wolfgang ; McIntosh, Andrew ; McLean, Alan ; Middeldorp, Christel M ; Middleton, Lefkos ; Montgomery, Grant M ; Murphy, Shawn N ; Nauck, Matthias ; Nolen, Willem A ; O'Donovan, Michael ; Oskarsson, Högni ; Pedersen, Nancy ; Scheftner, William A ; Schulz, Andrea ; Schulze, Thomas G ; Shyn, Stanley I ; Sigurdsson, Engilbert ; Slager, Susan L ; Smit, Johannes H ; Stefansson, Hreinn ; Steffens, Michael ; Thorgeirsson, Thorgeir ; Treutlein, Jens ; Uhr, Manfred ; van den Oord, Edwin J C G ; Van Grootheest, Gerard ; Völzke, Henry ; Weilburg, Jeffrey B ; Willemsen, Gonneke ; Daly, Mark ; Levinson, Douglas F ; Sullivan, Patrick F
Subjects: Adult and adolescent clinical studies ; Age ; Biological and medical sciences ; Bipolar disorder ; Bipolar Disorder - genetics ; Case-Control Studies ; Depression ; Depressive Disorder, Major - genetics ; Female ; Genetic aspects ; Genetic Predisposition to Disease - genetics ; Genome-wide association studies ; Genome-Wide Association Study - statistics & numerical data ; Genomes ; Genotyping ; Humans ; Independent sample ; Major depressive disorder ; Male ; Medical sciences ; Medicin och hälsovetenskap ; Mental depression ; Meta-analysis ; Mood disorders ; Polymorphism, Single Nucleotide - genetics ; Psychiatry ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Psykiatri ; Replication ; Risk factors ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Systematic review ; Whites - genetics
Is Part Of: Molecular psychiatry, 2013-04, Vol.18 (4), p.497-511
Description: 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.
Publisher: Basingstoke: Nature Publishing Group
Language: English
Identifier: ISSN: 1359-4184
ISSN: 1476-5578
EISSN: 1476-5578
DOI: 10.1038/mp.2012.21
PMID: 22472876
Source: ProQuest One Psychology
MEDLINE
SWEPUB Freely available online
ProQuest Central

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

2015 INIST-CNRS ;COPYRIGHT 2013 Nature Publishing Group ;Copyright Nature Publishing Group Apr 2013 ;Macmillan Publishers Limited 2013. ;2013 Macmillan Publishers Limited All rights reserved 2013 ;ISSN: 1359-4184 ;ISSN: 1476-5578 ;EISSN: 1476-5578 ;DOI: 10.1038/mp.2012.21 ;PMID: 22472876

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