Genome-wide association study identifies five new schizophrenia loci


Ripke, S; Sanders, AR; Kendler, KS; Levinson, DF; Sklar, P; Holmans, PA; Lin, DY; Duan, J; Ophoff, RA; Andreassen, OA; Scolnick, E; Cichon, S; Clair, DS; Corvin, A; Gurling, H; Werge, T; Rujescu, D; Blackwood, DHR; Pato, CN; Malhotra, AK; Purcell, S; Dudbridge, F; Neale, BM; Rossin, L; Visscher, PM; Posthuma, D; Ruderfer, DM; Fanous, A; Stefansson, H; Steinberg, S; Mowry, BJ; Golimbet, V; de Hert, M; Jonsson, EG; Bitter, I; Pietilainen, OPH; Collier, DA; Tosato, S; Agartz, I; Albus, M; Alexander, M; Amdur, RL; Amin, F; Bass, N; Bergen, SE; Black, DW; Borglum, AD; Brown, MA; Bruggeman, R; Buccola, NG; Byerley, WF; Cahn, W; Cantor, RM; Carr, VJ; Catts, SV; Choudhury, K; Cloninger, CR; Cormican, P; Craddock, N; Danoy, PA; Datta, S; de Haan, L; Demontis, D; Dikeos, D; Djurovic, S; Donnelly, P; Donohoe, G; Duong, L; Dwyer, S; Fink-Jensen, A; Freedman, R; Freimer, NB; Friedl, M; Georgieva, L; Giegling, I; Gill, M; Glenthoj, B; Godard, S; Hamshere, M; Hansen, M; Hansen, T; Hartmann, AM; Henskens, FA; Hougaard, DM; Hultman, CM; Ingason, A; Jablensky, AV; Jakobsen, KD; Jay, M; Jurgens, G; Kahn, R; Keller, MC; Kenis, G; Kenny, E; Kim, Y; Kirov, GK; Konnerth, H; Konte, B; Krabbendam, L; Krasucki, R; Lasseter, VK; Laurent, C; Lawrence, J; Lencz, T; Lerer, FB; Liang, KY; Lichtenstein, P; Lieberman, JA; Linszen, DH; Lonnqvist, J; Loughland, CM; MacLean, AW; Maher, BS; Maier, W; Mallet, J; Malloy, P; Mattheisen, M; Mattingsdal, M; McGhee, KA; McGrath, JJ; McIntosh, A; McLean, DE; McQuillin, A; Melle, I; Michie, PT; Milanova, V; Morris, DW; Mors, O; Mortensen, PB; Moskvina, V; Muglia, P; Myin-Germeys, I; Nertney, DA; Nestadt, G; Nielsen, J; Nikolov, I; Nordentoft, M; Norton, N; Nothen, MM; O'Dushlaine, CT; Olincy, A; Olsen, L; O'Neill, FA; Orntoft, TF; Owen, MJ; Pantelis, C; Papadimitriou, G; Pato, MT; Peltonen, L; Petursson, H; Pickard, B; Pimm, J; Pulver, AE; Puri, V; Quested, D; Quinn, EM; Rasmussen, HB; Rethelyi, JM; Ribble, R; Rietschel, M; Riley, BP; Ruggeri, M; Schall, U; Schulze, TG; Schwab, SG; Scott, RJ; Shi, JX; Sigurdsson, E; Silverman, JM; Spencer, CCA; Stefansson, K; Strange, A; Strengman, E; Stroup, TS; Suvisaari, J; Terenius, L; Thirumalai, S; Thygesen, JH; Timm, S; Toncheva, D; van Den Oord, E; van Os, J; van Winkel, R; Veldink, J; Walsh, D; Wang, AG; Wiersma, D; Wildenauer, DB; Williams, HJ; Williams, NM; Wormley, B; Zammit, S; Sullivan, PF; O'Donovan, MC; Daly, MJ; Gejman, PV; Schizophrenia Psychiat, G.-, W; (2011) Genome-wide association study identifies five new schizophrenia loci. Nature genetics, 43 (10). 969-U77. ISSN 1061-4036 DOI: https://doi.org/10.1038/ng.940

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Abstract

We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 x 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 x 10(-9)), ANK3 (rs10994359, P = 2.5 x 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 x 10(-9)).

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
PubMed ID: 21926974
Web of Science ID: 295316200011
URI: http://researchonline.lshtm.ac.uk/id/eprint/18596

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