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

Ripke, 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; Leeuw, De; 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, Sarah; Verhage, M; Walters, Jt; Multicenter Genetic Studies of Schizophrenia Consortium,; 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 Consortium,; 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,; 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; Spencer, Cc; 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, Cc; Bramon, E; Corvin, Ap; O'Donovan, Mc; Stefansson, K; Scolnick, E; Purcell, S; McCarroll, Sa; Sklar, P; Hultman, Cm; Sullivan, P. F.

doi:10.1038/ng.2742

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.

Titolo:	Genome-wide association analysis identifies 13 new risk loci for schizophrenia
Autori:	Ripke, 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, Sarah Verhage, M Walters, JT , Multicenter Genetic Studies of Schizophrenia Consortium 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 Consortium 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 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 Spencer, CC 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, CC Bramon, E Corvin, AP O'Donovan, MC Stefansson, K Scolnick, E Purcell, S McCarroll, SA Sklar, P Hultman, CM Sullivan, P.F. mostra contributor esterni nascondi contributor esterni
Data di pubblicazione:	2013
Rivista:	NATURE GENETICS
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.
Handle:	http://hdl.handle.net/11562/668558
Appare nelle tipologie:	01.01 Articolo in Rivista

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