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Nature genetics DOI:10.1038/ng.2742

Genome-wide association analysis identifies 13 new risk loci for schizophrenia.

Publication TypeJournal Article
Year of Publication2013
AuthorsRipke, S, O'Dushlaine, C, Chambert, K, Moran, JL, Kähler, AK, Akterin, S, Bergen, SE, Collins, AL, Crowley, JJ, Fromer, M, Kim, Y, Lee, SH, Magnusson, PK, Sanchez, N, Stahl, EA, Williams, S, Wray, NR, Xia, K, Bettella, F, Borglum, AD, Bulik-Sullivan, BK, Cormican, P, Craddock, N, de Leeuw, C, Durmishi, N, Gill, M, Golimbet, V, Hamshere, ML, Holmans, P, Hougaard, DM, Kendler, KS, Lin, K, Morris, DW, Mors, O, Mortensen, PB, Neale, BM, O'Neill, FA, Owen, MJ, Milovancevic, MP, Posthuma, D, Powell, J, Richards, AL, Riley, BP, Ruderfer, D, Rujescu, D, Sigurdsson, E, Silagadze, T, Smit, AB, Stefansson, H, Steinberg, S, Suvisaari, J, Tosato, S, Verhage, M, Walters, JT, Multicenter Genetic Studies of Schizophrenia, C, Levinson, DF, Gejman, PV, Kendler, KS, Laurent, C, Mowry, BJ, O'Donovan, MC, Owen, MJ, Pulver, AE, Riley, BP, Schwab, SG, Wildenauer, DB, Dudbridge, F, Holmans, P, Shi, J, Albus, M, Alexander, M, Campion, D, Cohen, D, Dikeos, D, Duan, J, Eichhammer, P, Godard, S, Hansen, M, Lerer, FB, Liang, KY, Maier, W, Mallet, J, Nertney, DA, Nestadt, G, Norton, N, O'Neill, FA, Papadimitriou, GN, Ribble, R, Sanders, AR, Silverman, JM, Walsh, D, Williams, NM, Wormley, B, Psychosis Endophenotypes International, C, Arranz, MJ, Bakker, S, Bender, S, Bramon, E, Collier, D, Crespo-Facorro, B, Hall, J, Iyegbe, C, Jablensky, A, Kahn, RS, Kalaydjieva, L, Lawrie, S, Lewis, CM, Lin, K, Linszen, DH, Mata, I, McIntosh, A, Murray, RM, Ophoff, RA, Powell, J, Rujescu, D, Van Os, J, Walshe, M, Weisbrod, M, Wiersma, D, Wellcome Trust Case Control Consortium, 2, Management, C:, Donnelly, P, Barroso, I, Blackwell, JM, Bramon, E, Brown, MA, Casas, JP, Corvin, AP, Deloukas, P, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CN, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Data and Analysis, G:, Spencer, CC, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, RD, Strange, A, Su, Z, Vukcevic, D, Donnelly, P, and DNA, Genotyping, DQCIG:, Langford, C, Hunt, SE, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, McCann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Tashakkori-Ghanbaria, A, Waller, MJ, Weston, P, Widaa, S, Whittaker, P, Barroso, I, Deloukas, P, Publications, C:, Mathew, CG, Blackwell, JM, Brown, MA, Corvin, AP, McCarthy, MI, Spencer, CC, Bramon, E, Corvin, AP, O'Donovan, MC, Stefansson, K, Scolnick, E, Purcell, S, McCarroll, SA, Sklar, P, Hultman, CM, Sullivan, PF
JournalNature genetics
Date Published2013/10/01

Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.