An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype
Creators: name: Bennett, David A.
name: Zhao, Wei
name: Lewis, Cathryn M.
name: Schulze, Thomas G.
name: De Jager, Philip L.
name: Nöthen, Markus M.
name: Demirkan, Ayse
name: Ladwig, Karl-Heinz
name: de Geus, Eco
name: Lahti, Jari
name: Rietschel, Marcella
name: Tiemeier, Henning
name: Uher, Rudolf
name: Martin, Nicholas G.
name: Murabito, Joanne M.
name: Amare, Azmeraw T.
name: Esko, Tonu
name: Kloiber, Stefan
name: Rice, John P.
name: Gill, Michael
name: Lucae, Susanne
name: Montgomery, Grant W.
name: Kutalik, Zoltán
name: Penninx, Brenda W.
name: Quiroz, Jorge A.
name: Jan Hottenga, Jouke
name: Faul, Jessica D.
name: Purcell, Shaun M.
name: Hartman, Catharina A.
name: van Duijn, Cornelia M.
name: Weissman, Myrna M.
name: Tanaka, Toshiko
name: Müller-Myhsok, Bertram
name: Fornage, Myriam
name: O'Donovan, Michael C.
name: Pergadia, Michele L.
name: Byrne, Enda M.
name: Kardia, Sharon L.R.
name: Direk, Nese
name: van Grootheest, Gerard
name: Domenici, Enrico
name: Horn, Carsten
name: Van der Auwera, Sandra
name: Smit, Johannes H.
name: Sullivan, Patrick F.
name: Boomsma, Dorret
name: Mosley, Thomas H.
name: Li, Qingqin S.
name: Lunetta, Kathryn L.
name: Lewis, Glyn
name: Potash, James B.
name: Buttenschøn, Henriette N.
name: Hek, Karin
name: Breen, Gerome
name: Shi, Jianxin
name: Clarke, Toni-Kim
name: Eriksson, Johan G.
name: Umbricht, Daniel
name: Preisig, Martin
name: Heath, Andrew C.
name: Homuth, Georg
name: Ferrucci, Luigi
name: Rivera, Margarita
name: Nyholt, Dale R.
name: Hamilton, Steven P.
name: Koenen, Karestan
name: Dunn, Erin C.
name: Baune, Bernhard T.
name: Willemsen, Gonneke
name: Weir, David R.
name: Levinson, Douglas F.
name: Yang, Jingyun
name: Perlis, Roy
name: Cichon, Sven
name: Dannlowski, Udo
name: Räikkönen, Katri
name: Ripke, Stephan
name: Smoller, Jordan W.
name: Mors, Ole
name: MacIntyre, Donald J.
name: Llewellyn, David J.
name: Tansey, Katherine E.
name: McIntosh, Andrew M.
name: Metspalu, Andres
name: Smith, Jennifer A.
name: Cornelis, Marilyn C.
name: Sinnamon, Grant C.
name: Ware, Erin B.
name: Teumer, Alexander
name: Shyn, Stanley
name: Air, Tracy
name: Blackwood, Douglas H.R.
name: Castelao, Enrique
name: Grabe, Hans Jörgen
name: Madden, Pamela
name: Gordon, Scott D.
name: Williams, Stephanie
name: Amin, Najaf
name: Hofman, Albert
name: Snieder, Harold
name: Børglum, Anders D.
name: Milaneschi, Yuri
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2017

description: AbstractBackgroundThe 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.