Journal article

An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype

Nese Direk, Stephanie Williams, Jennifer A Smith, Stephan Ripke, Tracy Air, Azmeraw T Amare, Najaf Amin, Bernhard T Baune, David A Bennett, Douglas HR Blackwood, Dorret Boomsma, Gerome Breen, Henriette N Buttenschon, Enda M Byrne, Anders D Borglum, Enrique Castelao, Sven Cichon, Toni-Kim Clarke, Marilyn C Cornelis, Udo Dannlowski Show all



BACKGROUND: The genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder. METHODS: We analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide pol..

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University of Melbourne Researchers


Awarded by U.S. National Institute of Mental Health

Awarded by National Institute of Mental Health

Awarded by NIA

Awarded by Swiss National Science Foundation

Awarded by German Research Foundation

Awarded by Innovative Medizinische Forschung of the Medical Faculty of Muenster

Awarded by Wellcome Trust

Awarded by Senior Clinical Fellowship

Awarded by Medical Research Council

Awarded by Innovative Medicine Initiative Joint Undertaking

Awarded by Netherlands Bioinformatics Centre/BioAssist/RK

Awarded by Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL)

Awarded by European Science Foundation

Awarded by European Network of Genomic and Genetic Epidemiology

Awarded by European Science Council (ERC)

Awarded by Rutgers University Cell and DNA Repository

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Awarded by Medical Research Council (U.K.)

Awarded by GlaxoSmithKline

Awarded by European Commission (EC)

Awarded by Federal Ministry of Education and Research

Awarded by MRC



Awarded by Lundbeck Foundation

Funding Acknowledgements

We acknowledge the essential role of the CHARGE consortium in development and support of this manuscript. CHARGE members include the Netherlands' Rotterdam Study; the National Heart, Lung, and Blood Institute's Framingham Heart Study, Cardiovascular Health Study, and Atherosclerosis Risk in Communities Study; and the National Institute on Aging's (NIA) Iceland Age, Gene/Environment Susceptibility Study. Core funding for the PGC is from the U.S. National Institute of Mental Health (U01MH094421). The PGC was supported by the National Institute of Mental Health (NIMH R01 MH094421 and NIMH R01 MH094421). The Health and Retirement Study is supported by the NIA (NIA U01AG009740). The genotyping was funded separately by the NIA (RC2 AG036495 and RC4 AG039029). Our genotyping was conducted by the National Institutes of Health (NIH) Center for Inherited Disease Research at Johns Hopkins University. Genotyping quality control and final preparation of the data were performed by the Genetics Coordinating Center at the University of Washington. The CoLaus vertical bar PsyCoLaus study was and is supported by research grants from GlaxoSmithKline, the Faculty of Biology and Medicine of Lausanne, and the Swiss National Science Foundation (3200B0-105993, 3200B0-118308, 33CSCO-122661, 33CS30-139468, and 33CS30-148401). The University of Edinburgh is a charitable body, registered in Scotland, with registration number SC005336. UD was supported by grants of the German Research Foundation (Grant No. FOR 2107; DA1151/5-1) and Innovative Medizinische Forschung of the Medical Faculty of Muenster (Grant Nos. DA120903, DA111107, and DA211012). DJM is an NRS Research Fellow supported by the Chief Scientist Office. AMM is supported by the Wellcome Trust (104036/Z/14/Z), The Dr Mortimer and Theresa Sackler Foundation, and a Senior Clinical Fellowship (SCD/12). GENPOD was funded by the Medical Research Council (G0200243), and we acknowledge the other coinvestigators: Phil Cowen, David Nutt, Tim J. Peters, and Deborah Sharp. This study makes use of data generated by the Wellcome Trust Case-Control Consortium. A full list of the investigators who contributed to the generation of the data is available from Funding for the project was provided by the Wellcome Trust (076113, 085475, and 090355). NEWMEDS: The research leading to these results has received support from the Innovative Medicine Initiative Joint Undertaking (115008), of which resources are composed of European Union and European Federation of Pharmaceutical Industries and Associations in-kind contributions and financial contributions from the European Union's Seventh Framework Programme (FP7/2007-2013). Funding for the Netherlands Study of Depression and Anxiety and Netherlands Twin Registry studies was obtained from the Netherlands Organization for Scientific Research (NWO), Center for Medical Systems Biology (NWO Genomics), Netherlands Bioinformatics Centre/BioAssist/RK(2008.024), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL, 184.021.007); VU University's Institute for Health and Care Research and Neuroscience Campus Amsterdam; the European Science Foundation (EU/QLRT-2001-01254); the European Community's Seventh Framework Programme (FP7/2007-2013); European Network of Genomic and Genetic Epidemiology (HEALTH-F4-2007-201413); the European Science Council (ERC Advanced, 230374); Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06); the Avera Institute, Sioux Falls, South Dakota (USA); and the NIH (R01D0042157-01A and MH081802, Grand Opportunity grants 1RC2 MH089951 and 1RC2 MH089995). Part of the genotyping and analyses was funded by the Genetic Association Information Network of the Foundation for the National Institutes of Health. Computing was supported by BiG Grid, the Dutch e-Science Grid, which is financially supported by NWO. The RADIANT studies present independent research part funded by a joint grant from the Medical Research Council (U.K.) and GlaxoSmithKline (G0701420) and by financial support from the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at the South London and Maudsley NHS (National Health Service) Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. The Genome-based Therapeutic Drugs for Depression (GENDEP) project was funded by the European Commission Framework 6 grant (EC contract reference: LSHB-CT-2003-503428). Lundbeck provided nortriptyline and escitalopram for the GENDEP study. GlaxoSmithKline and the U.K. NIHR of the Department of Health contributed to the funding of the sample collection at the Institute of Psychiatry (London). The collection of samples and genotyping of the Danish control subjects was supported by grants from the Danish Strategic Research Council, the Stanley Research Foundation, and H. Lundbeck A/S, and we thank David M. Hougaard, Section of Neonatal Screening and Hormones, Statens Serum Institute, Copenhagen, Denmark; Preben Bo Mortensen, National Centre for Register-based Research, Aarhus University, Denmark; and the Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark. The Study of Health in Pomerania (SHIP)-TREND is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs, and the Social Ministry of the Federal State of Mecklenburg-West Pomerania, and the network Greifswald Approach to Individualized Medicine (GANI_MED) is funded by the Federal Ministry of Education and Research (03IS2061A). Genome-wide genotyping in SHIP-TREND-0 was supported by the Federal Ministry of Education and Research (03ZIK012). This work was also funded by the German Research Foundation (GR 1912/5-1). The Cognitive Function and Mood Study is supported by the Faculty of Health Science, University of Adelaide, Adelaide, Australia. We are grateful to the Janssen study volunteers for participating in the clinical studies, participating clinical investigators, and the staff for enabling patient recruitment and blood sample collection.