TY - JOUR KW - CHARGE consortium KW - Depressive symptoms KW - FHIT gene KW - Genome-wide association study KW - Major depressive disorder KW - Psychiatric Genomics Consortium UR - http://doi.org/10.1016/j.biopsych.2016.11.013 A1 - Direk, N A1 - Williams, S A1 - Smith, JA A1 - Ripke, S A1 - Air, T A1 - Amare, AT A1 - Amin, N A1 - Baune, BT A1 - Bennett, DA A1 - Blackwood, DH A1 - Boomsma, D A1 - Breen, G A1 - Buttenschøn, HN A1 - Byrne, EM A1 - Børglum, AD A1 - Castelao, E A1 - Cichon, S A1 - Clarke, TK A1 - Cornelis, MC A1 - Dannlowski, U A1 - De Jager, PL A1 - Demirkan, A A1 - Domenici, E A1 - van Duijn, CM A1 - Dunn, EC A1 - Eriksson, JG A1 - Esko, T A1 - Faul, JD A1 - Ferrucci, L A1 - Fornage, M A1 - de Geus, E A1 - Gill, M A1 - Gordon, SD A1 - Grabe, HJ A1 - van Grootheest, G A1 - Hamilton, SP A1 - Hartman, CA A1 - Heath, AC A1 - Hek, K A1 - Hofman, A A1 - Homuth, G A1 - Horn, C A1 - Jan Hottenga, J A1 - Kardia, SL A1 - Kloiber, S A1 - Koenen, K A1 - Kutalik, Z A1 - Ladwig, KH A1 - Lahti, J A1 - Levinson, DF A1 - Lewis, CM A1 - Lewis, G A1 - Li, QS A1 - Llewellyn, DJ A1 - Lucae, S A1 - Lunetta, KL A1 - MacIntyre, DJ A1 - Madden, P A1 - Martin, NG A1 - McIntosh, AM A1 - Metspalu, A A1 - Milaneschi, Y A1 - Montgomery, GW A1 - Mors, O A1 - Mosley, TH A1 - Murabito, JM A1 - Müller-Myhsok, B A1 - Nöthen, MM A1 - Nyholt, DR A1 - O'Donovan, MC A1 - Penninx, BW A1 - Pergadia, ML A1 - Perlis, R A1 - Potash, JB A1 - Preisig, M A1 - Purcell, SM A1 - Quiroz, JA A1 - Räikkönen, K A1 - Rice, JP A1 - Rietschel, M A1 - Rivera, M A1 - Schulze, TG A1 - Shi, J A1 - Shyn, S A1 - Sinnamon, GC A1 - Smit, JH A1 - Smoller, JW A1 - Snieder, H A1 - Tanaka, T A1 - Tansey, KE A1 - Teumer, A A1 - Uher, R A1 - Umbricht, D A1 - Van der Auwera, S A1 - Ware, EB A1 - Weir, DR A1 - Weissman, MM A1 - Willemsen, G A1 - Yang, J A1 - Zhao, W A1 - Tiemeier, H A1 - Sullivan, PF AV - public ID - discovery1536203 SP - 322 JF - Biological Psychiatry N2 - 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. VL - 82 SN - 1873-2402 EP - 329 N1 - © Society of Biological Psychiatry, 2016. This manuscript version is made available under a Creative Commons Attribution Non-commercial Non-derivative 4.0 International license (CC BY-NC-ND 4.0). This license allows you to share, copy, distribute and transmit the work for personal and non-commercial use providing author and publisher attribution is clearly stated. Further details about CC BY licenses are available at https://creativecommons.org/licenses/. Access may be initially restricted by the publisher. Y1 - 2017/09// TI - An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype IS - 5 ER -