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Nat Genet 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, SHong, Magnusson, PKE, 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, MPejovic, 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, 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, F Lerer, B, Liang, K-Y, 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, 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, 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, CNA, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC, Viswanathan, AC, Wood, NW, Spencer, CCA, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, RD, Strange, A, Su, Z, Vukcevic, D, Donnelly, P, 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, Mathew, CG, Blackwell, JM, Brown, MA, Corvin, AP, McCarthy, MI, Spencer, CCA, Bramon, E, Corvin, AP, O'Donovan, MC, Stefansson, K, Scolnick, E, Purcell, S, McCarroll, SA, Sklar, P, Hultman, CM, Sullivan, PF
Corporate AuthorsMulticenter Genetic Studies of Schizophrenia Consortium, Psychosis Endophenotypes International Consortium, Wellcome Trust Case Control Consortium 2
JournalNat Genet
Volume45
Issue10
Pages1150-9
Date Published2013 Oct
ISSN1546-1718
KeywordsCase-Control Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, Schizophrenia, Sweden
Abstract

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.

URLhttp://dx.doi.org/10.1038/ng.2742
DOI10.1038/ng.2742
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/23974872?dopt=Abstract

Alternate JournalNat. Genet.
PubMed ID23974872
PubMed Central IDPMC3827979
Grant ListR01 MH095034 / MH / NIMH NIH HHS / United States
095552 / / Wellcome Trust / United Kingdom
R01 MH077139 / MH / NIMH NIH HHS / United States
G0601635 / / Medical Research Council / United Kingdom
G1100583 / / Medical Research Council / United Kingdom
K01 MH094406 / MH / NIMH NIH HHS / United States
090532 / / Wellcome Trust / United Kingdom
G0701420 / / Medical Research Council / United Kingdom
085475/B/08/Z / / Wellcome Trust / United Kingdom
G0600429 / / Medical Research Council / United Kingdom
G0901310 / / Medical Research Council / United Kingdom
R01 MH083094 / MH / NIMH NIH HHS / United States
U01 MH094421 / MH / NIMH NIH HHS / United States
PDA/02/06/016 / / Department of Health / United Kingdom
G0800509 / / Medical Research Council / United Kingdom
G1000718 / / Medical Research Council / United Kingdom
085475/Z/08/Z / / Wellcome Trust / United Kingdom