Direk, NeseWilliams, StephanieSmith, Jennifer ARipke, StephanAir, TracyAmare, Azmeraw TAmin, NajafBaune, Bernhard TBennett, David ABlackwood, Douglas H RBoomsma, DorretBreen, GeromeButtenschøn, Henriette NByrne, Enda MBørglum, Anders DCastelao, EnriqueCichon, SvenClarke, Toni-KimCornelis, Marilyn CDannlowski, UdoDe Jager, Philip LDemirkan, AyseDomenici, Enricovan Duijn, Cornelia MDunn, Erin CEriksson, Johan GEsko, TonuFaul, Jessica DFerrucci, LuigiFornage, Myriamde Geus, EcoGill, MichaelGordon, Scott DGrabe, Hans Jörgenvan Grootheest, GerardHamilton, Steven PHartman, Catharina AHeath, Andrew CHek, KarinHofman, AlbertHomuth, GeorgHorn, CarstenJan Hottenga, JoukeKardia, Sharon L RKloiber, StefanKoenen, KarestanKutalik, ZoltánLadwig, Karl-HeinzLahti, JariLevinson, Douglas FLewis, Cathryn MLewis, GlynLi, Qingqin SLlewellyn, David JLucae, SusanneLunetta, Kathryn LMacIntyre, Donald JMadden, PamelaMartin, Nicholas GMcIntosh, Andrew MMetspalu, AndresMilaneschi, YuriMontgomery, Grant WMors, OleMosley, Thomas HMurabito, Joanne MMüller-Myhsok, BertramNöthen, Markus MNyholt, Dale RO'Donovan, Michael CPenninx, Brenda WPergadia, Michele LPerlis, RoyPotash, James BPreisig, MartinPurcell, Shaun MQuiroz, Jorge ARäikkönen, KatriRice, John PRietschel, MarcellaRivera, MargaritaSchulze, Thomas GShi, JianxinShyn, StanleySinnamon, Grant CSmit, Johannes HSmoller, Jordan WSnieder, HaroldTanaka, ToshikoTansey, Katherine ETeumer, AlexanderUher, RudolfUmbricht, DanielVan der Auwera, SandraWare, Erin BWeir, David RWeissman, Myrna MWillemsen, GonnekeYang, JingyunZhao, WeiTiemeier, HenningSullivan, Patrick F2023-01-252023-01-252016-12-08Direk N, Williams S, Smith JA, Ripke S, Air T, Amare AT, et al. An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype. Biol Psychiatry. 2017 Sep 1;82(5):322-329.http://hdl.handle.net/10668/10736The 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. 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. 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). 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.enCHARGE consortiumDepressive symptomsFHIT geneGenome-wide association studyMajor depressive disorderPsychiatric Genomics ConsortiumAcid Anhydride HydrolasesDepressionDepressive DisorderGenetic LociGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansNeoplasm ProteinsPhenotypeWhite Peopleresearch article28049566Restricted AccessDepresiónEstudio de asociación del Genoma completoFenotipoPoblación blancaPredisposición genética a la enfermedadProteínas de NeoplasiasTrastorno depresivoÁcido anhídridoHidrolasas10.1016/j.biopsych.2016.11.0131873-2402PMC5462867https://helda.helsinki.fi/bitstream/10138/297903/1/An_Analysis_of_Two_Genome_wide_Association.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5462867/pdf