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000826053 0247_ $$2doi$$a10.1016/j.biopsych.2016.11.013
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000826053 1001_ $$aDirek, Nese$$b0
000826053 245__ $$aAn Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype
000826053 260__ $$aAmsterdam [u.a.]$$bElsevier Science$$c2017
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000826053 520__ $$aBackgroundThe genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder.MethodsWe analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures.ResultsThe SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 × 10–9) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 × 10–9).ConclusionsThis large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression.
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000826053 7001_ $$aSmith, Jennifer A.$$b2
000826053 7001_ $$aRipke, Stephan$$b3
000826053 7001_ $$aAir, Tracy$$b4
000826053 7001_ $$aAmare, Azmeraw T.$$b5
000826053 7001_ $$aAmin, Najaf$$b6
000826053 7001_ $$aBaune, Bernhard T.$$b7
000826053 7001_ $$aBennett, David A.$$b8
000826053 7001_ $$aBlackwood, Douglas H. R.$$b9
000826053 7001_ $$aBoomsma, Dorret$$b10
000826053 7001_ $$aBreen, Gerome$$b11
000826053 7001_ $$aButtenschøn, Henriette N.$$b12
000826053 7001_ $$aByrne, Enda M.$$b13
000826053 7001_ $$aBørglum, Anders D.$$b14
000826053 7001_ $$aCastelao, Enrique$$b15
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000826053 7001_ $$aClarke, Toni-Kim$$b17
000826053 7001_ $$aCornelis, Marilyn C.$$b18
000826053 7001_ $$aDannlowski, Udo$$b19
000826053 7001_ $$aDe Jager, Philip L.$$b20
000826053 7001_ $$aDemirkan, Ayse$$b21
000826053 7001_ $$aDomenici, Enrico$$b22
000826053 7001_ $$avan Duijn, Cornelia M.$$b23
000826053 7001_ $$aDunn, Erin C.$$b24
000826053 7001_ $$aEriksson, Johan G.$$b25
000826053 7001_ $$aEsko, Tonu$$b26
000826053 7001_ $$aFaul, Jessica D.$$b27
000826053 7001_ $$aFerrucci, Luigi$$b28
000826053 7001_ $$aFornage, Myriam$$b29
000826053 7001_ $$ade Geus, Eco$$b30
000826053 7001_ $$aGill, Michael$$b31
000826053 7001_ $$aGordon, Scott D.$$b32
000826053 7001_ $$aGrabe, Hans Jörgen$$b33
000826053 7001_ $$avan Grootheest, Gerard$$b34
000826053 7001_ $$aHamilton, Steven P.$$b35
000826053 7001_ $$aHartman, Catharina A.$$b36
000826053 7001_ $$aHeath, Andrew C.$$b37
000826053 7001_ $$aHek, Karin$$b38
000826053 7001_ $$aHofman, Albert$$b39
000826053 7001_ $$aHomuth, Georg$$b40
000826053 7001_ $$aHorn, Carsten$$b41
000826053 7001_ $$aJan Hottenga, Jouke$$b42
000826053 7001_ $$aKardia, Sharon L. R.$$b43
000826053 7001_ $$aKloiber, Stefan$$b44
000826053 7001_ $$aKoenen, Karestan$$b45
000826053 7001_ $$aKutalik, Zoltán$$b46
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000826053 7001_ $$aLahti, Jari$$b48
000826053 7001_ $$aLevinson, Douglas F.$$b49
000826053 7001_ $$aLewis, Cathryn M.$$b50
000826053 7001_ $$aLewis, Glyn$$b51
000826053 7001_ $$aLi, Qingqin S.$$b52
000826053 7001_ $$aLlewellyn, David J.$$b53
000826053 7001_ $$aLucae, Susanne$$b54
000826053 7001_ $$aLunetta, Kathryn L.$$b55
000826053 7001_ $$aMacIntyre, Donald J.$$b56
000826053 7001_ $$aMadden, Pamela$$b57
000826053 7001_ $$aMartin, Nicholas G.$$b58
000826053 7001_ $$aMcIntosh, Andrew M.$$b59
000826053 7001_ $$aMetspalu, Andres$$b60
000826053 7001_ $$aMilaneschi, Yuri$$b61
000826053 7001_ $$aMontgomery, Grant W.$$b62
000826053 7001_ $$00000-0002-5660-0393$$aMors, Ole$$b63
000826053 7001_ $$aMosley, Thomas H.$$b64
000826053 7001_ $$aMurabito, Joanne M.$$b65
000826053 7001_ $$aMüller-Myhsok, Bertram$$b66
000826053 7001_ $$aNöthen, Markus M.$$b67
000826053 7001_ $$aNyholt, Dale R.$$b68
000826053 7001_ $$aO’Donovan, Michael C.$$b69
000826053 7001_ $$aPenninx, Brenda W.$$b70
000826053 7001_ $$aPergadia, Michele L.$$b71
000826053 7001_ $$aPerlis, Roy$$b72
000826053 7001_ $$aPotash, James B.$$b73
000826053 7001_ $$aPreisig, Martin$$b74
000826053 7001_ $$aPurcell, Shaun M.$$b75
000826053 7001_ $$aQuiroz, Jorge A.$$b76
000826053 7001_ $$aRäikkönen, Katri$$b77
000826053 7001_ $$aRice, John P.$$b78
000826053 7001_ $$aRietschel, Marcella$$b79
000826053 7001_ $$aRivera, Margarita$$b80
000826053 7001_ $$aSchulze, Thomas G.$$b81
000826053 7001_ $$aShi, Jianxin$$b82
000826053 7001_ $$00000-0002-5962-1237$$aShyn, Stanley$$b83
000826053 7001_ $$aSinnamon, Grant C.$$b84
000826053 7001_ $$aSmit, Johannes H.$$b85
000826053 7001_ $$aSmoller, Jordan W.$$b86
000826053 7001_ $$aSnieder, Harold$$b87
000826053 7001_ $$aTanaka, Toshiko$$b88
000826053 7001_ $$aTansey, Katherine E.$$b89
000826053 7001_ $$aTeumer, Alexander$$b90
000826053 7001_ $$aUher, Rudolf$$b91
000826053 7001_ $$aUmbricht, Daniel$$b92
000826053 7001_ $$aVan der Auwera, Sandra$$b93
000826053 7001_ $$aWare, Erin B.$$b94
000826053 7001_ $$aWeir, David R.$$b95
000826053 7001_ $$aWeissman, Myrna M.$$b96
000826053 7001_ $$aWillemsen, Gonneke$$b97
000826053 7001_ $$aYang, Jingyun$$b98
000826053 7001_ $$aZhao, Wei$$b99
000826053 7001_ $$00000-0002-4395-1397$$aTiemeier, Henning$$b100$$eCorresponding author
000826053 7001_ $$aSullivan, Patrick F.$$b101
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