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 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 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 Consortium None., 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 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., Psychosis Endophenotypes International Consortium None., 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 None., 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.
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.