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

Verfasser:	Direk, Nese Williams, Stephanie Smith, Jennifer A Ripke, Stephan Air, Tracy Amare, Azmeraw T Amin, Najaf Baune, Bernhard T Bennett, David A Blackwood, Douglas H R Boomsma, Dorret Breen, Gerome Buttenschøn, Henriette Nørmølle Byrne, Enda M Børglum, Anders D Castelao, Enrique Cichon, Sven Clarke, Toni-Kim Cornelis, Marilyn C Dannlowski, Udo De Jager, Philip L Demirkan, Ayse Domenici, Enrico van Duijn, Cornelia M Dunn, Erin C Eriksson, Johan G Esko, Tonu Faul, Jessica D Ferrucci, Luigi Fornage, Myriam de Geus, Eco Gill, Michael Gordon, Scott D Grabe, Hans-Jörgen van Grootheest, Gerard Hamilton, Steven P Hartman, Catharina A Heath, Andrew C Hek, Karin Hofman, Albert Homuth, Georg Horn, Carsten Jan Hottenga, Jouke Kardia, Sharon L R Kloiber, Stefan Koenen, Karestan Kutalik, Zoltán Ladwig, Karl-Heinz Lahti, Jari Levinson, Douglas F Lewis, Cathryn M Lewis, Glyn Li, Qingqin S Llewellyn, David J Lucae, Susanne Lunetta, Kathryn L MacIntyre, Donald J Madden, Pamela A F Martin, Nicholas G McIntosh, Andrew M Metspalu, Andres Milaneschi, Yuri Montgomery, Grant W Mors, Ole Mosley, Thomas H Murabito, Joanne M Müller-Myhsok, Bertram Nöthen, Markus M Nyholt, Dale R O'Donovan, Michael C Penninx, Brenda W Pergadia, Michele L. Perlis, Roy Potash, James B Preisig, Martin Purcell, Shaun M Quiroz, Jorge A Räikkönen, Katri Rice, John P Rietschel, Marcella Rivera, Margarita Schulze, Thomas G Shi, Jianxin Shyn, Stanley I Sinnamon, Grant C Smit, Johannes H Smoller, Jordan W Snieder, Harold Tanaka, Toshiko Tansey, Katherine E Teumer, Alexander Uher, Rudolf Umbricht, Daniel Van der Auwera, Sandra Ware, Erin B Weir, David R Weissman, Myrna M Willemsen, Gonneke Yang, Jingyun Zhao, Wei Tiemeier, Henning Sullivan, Patrick F
Dokumenttyp:	Artikel
Erscheinungsdatum:	2017
Reihe/Periodikum:	Direk , N , Williams , S , Smith , J A , Ripke , S , Air , T , Amare , A T , Amin , N , Baune , B T , Bennett , D A , Blackwood , D H R , Boomsma , D , Breen , G , Buttenschøn , H N , Byrne , E M , Børglum , A D , Castelao , E , Cichon , S , Clarke , T-K , Cornelis , M C , Dannlowski , U , De Jager , P L , Demirkan , A , Domenici , E , van Duijn , C M , Dunn , E C , Eriksson , J G , Esko , T , Faul , J D , Ferrucci , L , Fornage , M , de Geus , E , Gill , M , Gordon , S D , Grabe , H-J , van Grootheest , G , Hamilton , S P , Hartman , C A , Heath , A C , Hek , K , Hofman , A , Homuth , G , Horn , C , Jan Hottenga , J , Kardia , S L R , Kloiber , S , Koenen , K , Kutalik , Z , Ladwig , K-H , Lahti , J , Levinson , D F , Lewis , C M , Lewis , G , Li , Q S , Llewellyn , D J , Lucae , S , Lunetta , K L , MacIntyre , D J , Madden , P A F , Martin , N G , McIntosh , A M , Metspalu , A , Milaneschi , Y , Montgomery , G W , Mors , O , Mosley , T H , Murabito , J M , Müller-Myhsok , B , Nöthen , M M , Nyholt , D R , O'Donovan , M C , Penninx , B W , Pergadia , M L , Perlis , R , Potash , J B , Preisig , M , Purcell , S M , Quiroz , J A , Räikkönen , K , Rice , J P , Rietschel , M , Rivera , M , Schulze , T G , Shi , J , Shyn , S I , Sinnamon , G C , Smit , J H , Smoller , J W , Snieder , H , Tanaka , T , Tansey , K E , Teumer , A , Uher , R , Umbricht , D , Van der Auwera , S , Ware , E B , Weir , D R , Weissman , M M , Willemsen , G , Yang , J , Zhao , W , Tiemeier , H & Sullivan , P F 2017 , ' An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype ' , Biological Psychiatry , vol. 82 , no. 5 , pp. 322-329 . https://doi.org/10.1016/j.biopsych.2016.11.013
Schlagwörter:	Journal Article / /dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_ / name=Netherlands Twin Register (NTR) / /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being / name=SDG 3 - Good Health and Well-being
Sprache:	Englisch
Permalink:	https://search.fid-benelux.de/Record/base-26845237
Datenquelle:	BASE; Originalkatalog
Powered By:	BASE
Link(s) :	https://research.vu.nl/en/publications/d6772206-da14-42ac-ab91-6dbe89ebb60a

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 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. RESULTS: The 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)). CONCLUSIONS: This 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.