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