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DOI: 10.1038/mp.2012.21
¤ OpenAccess: Bronze
This work has “Bronze” OA status. This means it is free to read on the publisher landing page, but without any identifiable license.
A mega-analysis of genome-wide association studies for major depressive disorder
Stephan Ripke,Naomi R. Wray,Cathryn M. Lewis,Steven P. Hamilton,Myrna M. Weissman,Gerome Breen,Enda M. Byrne,Douglas Blackwood,Dorret I. Boomsma,Sven Cichon,Andrew C. Heath,Florian Holsboer,Susanne Lucae,Pamela A. F. Madden,Nicholas G. Martin,Peter McGuffin,Pierandrea Muglia,Markus M. Nöethen,Brenda Penninx,Michele L. Pergadia,James B. Potash,Marcella Rietschel,Danyu Lin,Bertram Müller‐Myhsok,Jianxin Shi,Stacy Steinberg,Hans J. Grabe,Paul Lichtenstein,Patrik K. E. Magnusson,Roy H. Perlis,Martin Preisig,Jordan W. Smoller,Kāri Stefánsson,Rudolf Uher,Zoltán Kutalik,Katherine E. Tansey,Alexander Teumer,Alexander Viktorin,Michael R. Barnes,Thomas Bettecken,Elisabeth B. Binder,René Breuer,Víctor M. Castro,Susanne Churchill,William Coryell,Nicholas John Craddock,Ian W. Craig,Darina Czamara,Eco J. C. de Geus,Franziska Degenhardt,Anne Farmer,Maurizio Fava,Josef Frank,Vivian S. Gainer,Patience Gallagher,Scott D. Gordon,Sergey Goryachev,Magdalena Groß,Michel Guipponi,Anjali K. Henders,Stefan Herms,Ian B. Hickie,Susanne Hoefels,Witte J.G. Hoogendijk,Jouke Jan Hottenga,Dan V. Iosifescu,Marcus Ising,Ian Jones,Lisa Jones,Jung-Ying Tzeng,James A. Knowles,Isaac S. Kohane,Martin Kohli,Ania Korszun,Mikael Landén,William B. Lawson,Glyn Lewis,Donald J. MacIntyre,Wolfgang Maier,Manuel Mattheisen,Patrick J. McGrath,Andrew M. McIntosh,Alan W. McLean,Christel M. Middeldorp,Lefkos Middleton,Grant Montgomery,Shawn N. Murphy,Matthias Nauck,Willem A. Nolen,Dale R. Nyholt,Michael Conlon O'Donovan,Högni Óskarsson,Nancy L. Pedersen,William A. Scheftner,Andrea Schulz,Thomas G. Schulze,Stanley I. Shyn,Engilbert Sigurðsson,Susan L. Slager,Johannes H. Smit,Hreinn Stefánsson,Michael Steffens,Thorgeir E. Thorgeirsson,Federica Tozzi,Jens Treutlein,Manfred Uhr,Edwin J. C. G. van den Oord,Gerard van Grootheest,Henry Völzke,Jeffrey B. Weilburg,Gonneke Willemsen,Frans G. Zitman,Benjamin M. Neale,Mark J. Daly,Douglas F. Levinson,Patrick F. Sullivan
Major depressive disorder
Genome-wide association study
Single-nucleotide polymorphism
2012
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.
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“A mega-analysis of genome-wide association studies for major depressive disorder” is a paper by Stephan Ripke Naomi R. Wray Cathryn M. Lewis Steven P. Hamilton Myrna M. Weissman Gerome Breen Enda M. Byrne Douglas Blackwood Dorret I. Boomsma Sven Cichon Andrew C. Heath Florian Holsboer Susanne Lucae Pamela A. F. Madden Nicholas G. Martin Peter McGuffin Pierandrea Muglia Markus M. Nöethen Brenda Penninx Michele L. Pergadia James B. Potash Marcella Rietschel Danyu Lin Bertram Müller‐Myhsok Jianxin Shi Stacy Steinberg Hans J. Grabe Paul Lichtenstein Patrik K. E. Magnusson Roy H. Perlis Martin Preisig Jordan W. Smoller Kāri Stefánsson Rudolf Uher Zoltán Kutalik Katherine E. Tansey Alexander Teumer Alexander Viktorin Michael R. Barnes Thomas Bettecken Elisabeth B. Binder René Breuer Víctor M. Castro Susanne Churchill William Coryell Nicholas John Craddock Ian W. Craig Darina Czamara Eco J. C. de Geus Franziska Degenhardt Anne Farmer Maurizio Fava Josef Frank Vivian S. Gainer Patience Gallagher Scott D. Gordon Sergey Goryachev Magdalena Groß Michel Guipponi Anjali K. Henders Stefan Herms Ian B. Hickie Susanne Hoefels Witte J.G. Hoogendijk Jouke Jan Hottenga Dan V. Iosifescu Marcus Ising Ian Jones Lisa Jones Jung-Ying Tzeng James A. Knowles Isaac S. Kohane Martin Kohli Ania Korszun Mikael Landén William B. Lawson Glyn Lewis Donald J. MacIntyre Wolfgang Maier Manuel Mattheisen Patrick J. McGrath Andrew M. McIntosh Alan W. McLean Christel M. Middeldorp Lefkos Middleton Grant Montgomery Shawn N. Murphy Matthias Nauck Willem A. Nolen Dale R. Nyholt Michael Conlon O'Donovan Högni Óskarsson Nancy L. Pedersen William A. Scheftner Andrea Schulz Thomas G. Schulze Stanley I. Shyn Engilbert Sigurðsson Susan L. Slager Johannes H. Smit Hreinn Stefánsson Michael Steffens Thorgeir E. Thorgeirsson Federica Tozzi Jens Treutlein Manfred Uhr Edwin J. C. G. van den Oord Gerard van Grootheest Henry Völzke Jeffrey B. Weilburg Gonneke Willemsen Frans G. Zitman Benjamin M. Neale Mark J. Daly Douglas F. Levinson Patrick F. Sullivan published in 2012. It has an Open Access status of “bronze”. You can read and download a PDF Full Text of this paper here.