%0 Journal Article
%A Direk, Nese
%A Williams, Stephanie
%A Smith, Jennifer A.
%A Ripke, Stephan
%A Air, Tracy
%A Amare, Azmeraw T.
%A Amin, Najaf
%A Baune, Bernhard T.
%A Bennett, David A.
%A Blackwood, Douglas H. R.
%A Boomsma, Dorret
%A Breen, Gerome
%A Buttenschøn, Henriette N.
%A Byrne, Enda M.
%A Børglum, Anders D.
%A Castelao, Enrique
%A Cichon, Sven
%A Clarke, Toni-Kim
%A Cornelis, Marilyn C.
%A Dannlowski, Udo
%A De Jager, Philip L.
%A Demirkan, Ayse
%A Domenici, Enrico
%A van Duijn, Cornelia M.
%A Dunn, Erin C.
%A Eriksson, Johan G.
%A Esko, Tonu
%A Faul, Jessica D.
%A Ferrucci, Luigi
%A Fornage, Myriam
%A de Geus, Eco
%A Gill, Michael
%A Gordon, Scott D.
%A Grabe, Hans Jörgen
%A van Grootheest, Gerard
%A Hamilton, Steven P.
%A Hartman, Catharina A.
%A Heath, Andrew C.
%A Hek, Karin
%A Hofman, Albert
%A Homuth, Georg
%A Horn, Carsten
%A Jan Hottenga, Jouke
%A Kardia, Sharon L. R.
%A Kloiber, Stefan
%A Koenen, Karestan
%A Kutalik, Zoltán
%A Ladwig, Karl-Heinz
%A Lahti, Jari
%A Levinson, Douglas F.
%A Lewis, Cathryn M.
%A Lewis, Glyn
%A Li, Qingqin S.
%A Llewellyn, David J.
%A Lucae, Susanne
%A Lunetta, Kathryn L.
%A MacIntyre, Donald J.
%A Madden, Pamela
%A Martin, Nicholas G.
%A McIntosh, Andrew M.
%A Metspalu, Andres
%A Milaneschi, Yuri
%A Montgomery, Grant W.
%A Mors, Ole
%A Mosley, Thomas H.
%A Murabito, Joanne M.
%A Müller-Myhsok, Bertram
%A Nöthen, Markus M.
%A Nyholt, Dale R.
%A O’Donovan, Michael C.
%A Penninx, Brenda W.
%A Pergadia, Michele L.
%A Perlis, Roy
%A Potash, James B.
%A Preisig, Martin
%A Purcell, Shaun M.
%A Quiroz, Jorge A.
%A Räikkönen, Katri
%A Rice, John P.
%A Rietschel, Marcella
%A Rivera, Margarita
%A Schulze, Thomas G.
%A Shi, Jianxin
%A Shyn, Stanley
%A Sinnamon, Grant C.
%A Smit, Johannes H.
%A Smoller, Jordan W.
%A Snieder, Harold
%A Tanaka, Toshiko
%A Tansey, Katherine E.
%A Teumer, Alexander
%A Uher, Rudolf
%A Umbricht, Daniel
%A Van der Auwera, Sandra
%A Ware, Erin B.
%A Weir, David R.
%A Weissman, Myrna M.
%A Willemsen, Gonneke
%A Yang, Jingyun
%A Zhao, Wei
%A Tiemeier, Henning
%A Sullivan, Patrick F.
%T An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype
%J Biological psychiatry
%V 82
%N 5
%@ 0006-3223
%C Amsterdam [u.a.]
%I Elsevier Science
%M FZJ-2017-00322
%P 322-329
%D 2017
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%U <Go to ISI:>//WOS:000406938900010
%$ pmid:28049566
%R 10.1016/j.biopsych.2016.11.013
%U https://juser.fz-juelich.de/record/826053