Title | An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Direk, N, Williams, S, Smith, JA, Ripke, S, Air, T, Amare, AT, Amin, N, Baune, BT, Bennett, DA, Blackwood, DHR, Boomsma, DI, Breen, G, Buttenschøn, HN, Byrne, EM, Børglum, AD, Castelao, E, Cichon, S, Clarke, T-K, Cornelis, MC, Dannlowski, U, de Jager, PL, Demirkan, A, Domenici, E, van Duijn, CM, Dunn, EC, Eriksson, JG, Esko, T, Faul, J, Ferrucci, L, Fornage, M, de Geus, EJC, Gill, M, Gordon, SD, Grabe, H-J, van Grootheest, G, Hamilton, SP, Hartman, CA, Heath, AC, Hek, K, Hofman, A, Homuth, G, Horn, C, Hottenga, J-J, Kardia, SLR, Kloiber, S, Koenen, KC, Kutalik, Z, Ladwig, K-H, Lahti, J, Levinson, DF, Lewis, CM, Lewis, G, Li, QS, Llewellyn, DJ, Lucae, S, Lunetta, KL, MacIntyre, DJ, Madden, PAF, Martin, NG, McIntosh, AM, Metspalu, A, Milaneschi, Y, Montgomery, GW, Mors, O, Mosley, TH, Murabito, JM, Müller-Myhsok, B, Nöthen, MM, Nyholt, DR, O'Donovan, MC, Penninx, BWJH, Pergadia, ML, Perlis, R, Potash, JB, Preisig, M, Purcell, SM, Quiroz, JA, Räikkönen, K, Rice, JP, Rietschel, M, Rivera, M, Schulze, TG, Shi, J, Shyn, S, Sinnamon, GC, Smit, JH, Smoller, JW, Snieder, H, Tanaka, T, Tansey, KE, Teumer, A, Uher, R, Umbricht, D, Van der Auwera, S, Ware, EB, Weir, DR, Weissman, MM, Willemsen, G, Yang, J, Zhao, W, Tiemeier, H, Sullivan, PF |
Journal | Biological Psychiatry |
Volume | 82 |
Issue | 5 |
Pagination | 322-329 |
ISSN Number | 1873-2402 |
Keywords | Acid Anhydride Hydrolases, depression, Depressive Disorder, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Neoplasm Proteins, Phenotype, Whites |
Abstract | 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) 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). 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. |
DOI | 10.1016/j.biopsych.2016.11.013 |
Citation Key | 12135 |
PubMed ID | 28049566 |
PubMed Central ID | PMC5462867 |
Grant List | R01 MH095034 / MH / NIMH NIH HHS / United States U01 AG009740 / AG / NIA NIH HHS / United States G0200243 / MRC_ / Medical Research Council / United Kingdom 076113 / / Wellcome Trust / United Kingdom G0701420 / / Medical Research Council / United Kingdom U24 MH068457 / MH / NIMH NIH HHS / United States U01 MH094421 / MH / NIMH NIH HHS / United States 090355 / / Wellcome Trust / United Kingdom U01 MH109528 / MH / NIMH NIH HHS / United States MR/K026992/1 / MRC_ / Medical Research Council / United Kingdom RC2 MH089951 / MH / NIMH NIH HHS / United States RC4 AG039029 / AG / NIA NIH HHS / United States R01 MH081802 / MH / NIMH NIH HHS / United States RF1 AG015819 / AG / NIA NIH HHS / United States RC2 MH089995 / MH / NIMH NIH HHS / United States R01 MH077139 / MH / NIMH NIH HHS / United States 104036 / / Wellcome Trust / United Kingdom R01 AG017917 / AG / NIA NIH HHS / United States / / Department of Health / United Kingdom 085475 / / Wellcome Trust / United Kingdom P30 AG010161 / AG / NIA NIH HHS / United States K01 MH102403 / MH / NIMH NIH HHS / United States RC2 AG036495 / AG / NIA NIH HHS / United States / / Wellcome Trust / United Kingdom |