TY  - JOUR
AU  - Direk, Nese
AU  - Williams, Stephanie
AU  - Smith, Jennifer A.
AU  - Ripke, Stephan
AU  - Air, Tracy
AU  - Amare, Azmeraw T.
AU  - Amin, Najaf
AU  - Baune, Bernhard T.
AU  - Bennett, David A.
AU  - Blackwood, Douglas H. R.
AU  - Boomsma, Dorret
AU  - Breen, Gerome
AU  - Buttenschøn, Henriette N.
AU  - Byrne, Enda M.
AU  - Børglum, Anders D.
AU  - Castelao, Enrique
AU  - Cichon, Sven
AU  - Clarke, Toni-Kim
AU  - Cornelis, Marilyn C.
AU  - Dannlowski, Udo
AU  - De Jager, Philip L.
AU  - Demirkan, Ayse
AU  - Domenici, Enrico
AU  - van Duijn, Cornelia M.
AU  - Dunn, Erin C.
AU  - Eriksson, Johan G.
AU  - Esko, Tonu
AU  - Faul, Jessica D.
AU  - Ferrucci, Luigi
AU  - Fornage, Myriam
AU  - de Geus, Eco
AU  - Gill, Michael
AU  - Gordon, Scott D.
AU  - Grabe, Hans Jörgen
AU  - van Grootheest, Gerard
AU  - Hamilton, Steven P.
AU  - Hartman, Catharina A.
AU  - Heath, Andrew C.
AU  - Hek, Karin
AU  - Hofman, Albert
AU  - Homuth, Georg
AU  - Horn, Carsten
AU  - Jan Hottenga, Jouke
AU  - Kardia, Sharon L. R.
AU  - Kloiber, Stefan
AU  - Koenen, Karestan
AU  - Kutalik, Zoltán
AU  - Ladwig, Karl-Heinz
AU  - Lahti, Jari
AU  - Levinson, Douglas F.
AU  - Lewis, Cathryn M.
AU  - Lewis, Glyn
AU  - Li, Qingqin S.
AU  - Llewellyn, David J.
AU  - Lucae, Susanne
AU  - Lunetta, Kathryn L.
AU  - MacIntyre, Donald J.
AU  - Madden, Pamela
AU  - Martin, Nicholas G.
AU  - McIntosh, Andrew M.
AU  - Metspalu, Andres
AU  - Milaneschi, Yuri
AU  - Montgomery, Grant W.
AU  - Mors, Ole
AU  - Mosley, Thomas H.
AU  - Murabito, Joanne M.
AU  - Müller-Myhsok, Bertram
AU  - Nöthen, Markus M.
AU  - Nyholt, Dale R.
AU  - O’Donovan, Michael C.
AU  - Penninx, Brenda W.
AU  - Pergadia, Michele L.
AU  - Perlis, Roy
AU  - Potash, James B.
AU  - Preisig, Martin
AU  - Purcell, Shaun M.
AU  - Quiroz, Jorge A.
AU  - Räikkönen, Katri
AU  - Rice, John P.
AU  - Rietschel, Marcella
AU  - Rivera, Margarita
AU  - Schulze, Thomas G.
AU  - Shi, Jianxin
AU  - Shyn, Stanley
AU  - Sinnamon, Grant C.
AU  - Smit, Johannes H.
AU  - Smoller, Jordan W.
AU  - Snieder, Harold
AU  - Tanaka, Toshiko
AU  - Tansey, Katherine E.
AU  - Teumer, Alexander
AU  - Uher, Rudolf
AU  - Umbricht, Daniel
AU  - Van der Auwera, Sandra
AU  - Ware, Erin B.
AU  - Weir, David R.
AU  - Weissman, Myrna M.
AU  - Willemsen, Gonneke
AU  - Yang, Jingyun
AU  - Zhao, Wei
AU  - Tiemeier, Henning
AU  - Sullivan, Patrick F.
TI  - An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype
JO  - Biological psychiatry
VL  - 82
IS  - 5
SN  - 0006-3223
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - FZJ-2017-00322
SP  - 322-329
PY  - 2017
AB  - 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.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000406938900010
C6  - pmid:28049566
DO  - DOI:10.1016/j.biopsych.2016.11.013
UR  - https://juser.fz-juelich.de/record/826053
ER  -