Home > Publications database > An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype > print

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024 7 _ |a 10.1016/j.biopsych.2016.11.013
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024 7 _ |a 1873-2402
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037 _ _ |a FZJ-2017-00322
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Direk, Nese
|b 0
245 _ _ |a An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype
260 _ _ |a Amsterdam [u.a.]
|c 2017
|b Elsevier Science
336 7 _ |a article
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336 7 _ |a ARTICLE
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520 _ _ |a BackgroundThe 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.MethodsWe 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 polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures.ResultsThe SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 × 10–9) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 × 10–9).ConclusionsThis large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression.
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700 1 _ |a Williams, Stephanie
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700 1 _ |a Smith, Jennifer A.
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700 1 _ |a Ripke, Stephan
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700 1 _ |a Dunn, Erin C.
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700 1 _ |a Esko, Tonu
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700 1 _ |a Ferrucci, Luigi
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700 1 _ |a Fornage, Myriam
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700 1 _ |a de Geus, Eco
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700 1 _ |a Gill, Michael
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700 1 _ |a Gordon, Scott D.
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700 1 _ |a van Grootheest, Gerard
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700 1 _ |a Hek, Karin
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700 1 _ |a Hofman, Albert
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700 1 _ |a Lewis, Cathryn M.
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700 1 _ |a Lewis, Glyn
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700 1 _ |a Li, Qingqin S.
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700 1 _ |a Llewellyn, David J.
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700 1 _ |a Martin, Nicholas G.
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700 1 _ |a McIntosh, Andrew M.
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700 1 _ |a Metspalu, Andres
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700 1 _ |a Milaneschi, Yuri
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700 1 _ |a Mosley, Thomas H.
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700 1 _ |a Murabito, Joanne M.
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700 1 _ |a Müller-Myhsok, Bertram
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700 1 _ |a Nöthen, Markus M.
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700 1 _ |a Nyholt, Dale R.
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700 1 _ |a O’Donovan, Michael C.
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700 1 _ |a Penninx, Brenda W.
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700 1 _ |a Pergadia, Michele L.
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700 1 _ |a Perlis, Roy
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700 1 _ |a Potash, James B.
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700 1 _ |a Preisig, Martin
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700 1 _ |a Purcell, Shaun M.
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700 1 _ |a Quiroz, Jorge A.
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700 1 _ |a Räikkönen, Katri
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700 1 _ |a Rice, John P.
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700 1 _ |a Rietschel, Marcella
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700 1 _ |a Rivera, Margarita
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700 1 _ |a Shyn, Stanley
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700 1 _ |a Sinnamon, Grant C.
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700 1 _ |a Sullivan, Patrick F.
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