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

Autoria(s): Ripke, S.; O'Dushlaine, C.; Chambert, K.; Moran, J. L.; Kähler, A. K.; Akterin, S.; Bergen, S. E.; Collins, A. L.; Crowley, J. J.; Fromer, M.; Kim, Y.; Lee, S. H.; Magnusson, P. K. E.; Sanchez, N.; Stahl, E. A.; Williams, S.; Wray, N. R.; Xia, K.; Bettella, F.; Borglum, A. D.; Bulik-Sullivan, B. K.; Cormican, P.; Craddock, N.; De Leeuw, C.; Durmishi, N.; Gill, M.; Golimbet, V.; Hamshere, M. L.; Holmans, P.; Hougaard, D. M.; Kendler, K. S.; Lin, K.; Morris, D. W.; Mors, O.; Mortensen, P. B.; Neale, B. M.; O'Neill, F. A.; Owen, M. J.; Milovancevic, M. P.; Posthuma, D.; Powell, J.; Richards, A. L.; Riley, B. P.; Ruderfer, D.; Sigurdsson, E.; Silagadze, T.; Smit, A. B.; Stefansson, H.; Steinberg, S.; Suvisaari, J.; Tosato, S.; Verhage, M.; Walters, J. T.; Levinson, D. F.; Gejman, P. V.; Laurent, C.; Mowry, B. J.; O'Donovan, M. C.; Pulver, A. E.; Schwab, S. G.; Wildenauer, D. B.; Dudbridge, F.; Shi, J.; Albus, M.; Alexander, M.; Campion, D.; Cohen, D.; Dikeos, D.; Duan, J.; Eichhammer, P.; Godard, S.; Hansen, M.; Lerer, F. B.; Liang, K. Y.; Maier, W.; Mallet, J.; Nertney, D. A.; Nestadt, G.; Norton, N.; Papadimitriou, G. N.; Ribble, R.; Sanders, A. R.; Silverman, J. M.; Walsh, D.; Williams, N. M.; Wormley, B.; Arranz, M. J.; Bakker, S.; Bender, S.; Bramon, E.; Collier, D.; Crespo-Facorro, B.; Hall, J.; Iyegbe, C.; Jablensky, A.; Kahn, R. S.; Kalaydjieva, L.; Lawrie, S.; Lewis, C. M.; Linszen, D. H.; Mata, I.; McIntosh, A.; Murray, R. M.; Ophoff, R. A.; Rujescu, D.; Van Os, J.; Walshe, M.; Weisbrod, M.; Wiersma, D.; Donnelly, P.; Blackwell, J. M.; Brown, M.A.; Casas, J. P.; Corvin, A. P.; Duncanson, A.; Jankowski, J.; Markus, H. S.; Mathew, C. G.; Palmer, C. N. A.; Plomin, R.; Rautanen, A.; Sawcer, S. J.; Trembath, R. C.; Viswanathan, A. C.; Wood, N. W.; Spencer, C. C. A.; Band, G.; Bellenguez, C.; Freeman, C.; Hellenthal, G.; Giannoulatou, E.; Pirinen, M.; Pearson, R. D.; Strange, A.; Su, Z.; Vukcevic, D.; Langford, C.; Hunt, S. E.; Edkins, S.; Gwilliam, R.; Blackburn, H.; Bumpstead, S. J.; Dronov, S.; Gillman, M.; Gray, E.; Hammond, N.; Jayakumar, A.; McCann, O. T.; Liddle, J.; Potter, S. C.; Ravindrarajah, R.; Ricketts, M.; Tashakkori-Ghanbaria, A.; Waller, M. J.; Weston, P.; Widaa, S.; Whittaker, P.; Barroso, I.; Deloukas, P.; McCarthy, M. I.; Stefansson, K.; Scolnick, E.; Purcell, S.; McCarroll, S. A.; Sklar, P.; Hultman, C. M.; Sullivan, P. F.
Data(s)

2013
Resumo

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.
Identificador

http://eprints.qut.edu.au/89278/
Publicador

Nature Publishing Group
Relação

DOI:10.1038/ng.2742

Ripke, S., O'Dushlaine, C., Chambert, K., Moran, J. L., Kähler, A. K., Akterin, S., Bergen, S. E., Collins, A. L., Crowley, J. J., Fromer, M., Kim, Y., Lee, S. H., Magnusson, P. K. E., Sanchez, N., Stahl, E. A., Williams, S., Wray, N. R., Xia, K., Bettella, F., Borglum, A. D., Bulik-Sullivan, B. K., Cormican, P., Craddock, N., De Leeuw, C., Durmishi, N., Gill, M., Golimbet, V., Hamshere, M. L., Holmans, P., Hougaard, D. M., Kendler, K. S., Lin, K., Morris, D. W., Mors, O., Mortensen, P. B., Neale, B. M., O'Neill, F. A., Owen, M. J., Milovancevic, M. P., Posthuma, D., Powell, J., Richards, A. L., Riley, B. P., Ruderfer, D., Sigurdsson, E., Silagadze, T., Smit, A. B., Stefansson, H., Steinberg, S., Suvisaari, J., Tosato, S., Verhage, M., Walters, J. T., Levinson, D. F., Gejman, P. V., Laurent, C., Mowry, B. J., O'Donovan, M. C., Pulver, A. E., Schwab, S. G., Wildenauer, D. B., Dudbridge, F., Shi, J., Albus, M., Alexander, M., Campion, D., Cohen, D., Dikeos, D., Duan, J., Eichhammer, P., Godard, S., Hansen, M., Lerer, F. B., Liang, K. Y., Maier, W., Mallet, J., Nertney, D. A., Nestadt, G., Norton, N., Papadimitriou, G. N., Ribble, R., Sanders, A. R., Silverman, J. M., Walsh, D., Williams, N. M., Wormley, B., Arranz, M. J., Bakker, S., Bender, S., Bramon, E., Collier, D., Crespo-Facorro, B., Hall, J., Iyegbe, C., Jablensky, A., Kahn, R. S., Kalaydjieva, L., Lawrie, S., Lewis, C. M., Linszen, D. H., Mata, I., McIntosh, A., Murray, R. M., Ophoff, R. A., Rujescu, D., Van Os, J., Walshe, M., Weisbrod, M., Wiersma, D., Donnelly, P., Blackwell, J. M., Brown, M.A., Casas, J. P., Corvin, A. P., Duncanson, A., Jankowski, J., Markus, H. S., Mathew, C. G., Palmer, C. N. A., Plomin, R., Rautanen, A., Sawcer, S. J., Trembath, R. C., Viswanathan, A. C., Wood, N. W., Spencer, C. C. A., Band, G., Bellenguez, C., Freeman, C., Hellenthal, G., Giannoulatou, E., Pirinen, M., Pearson, R. D., Strange, A., Su, Z., Vukcevic, D., Langford, C., Hunt, S. E., Edkins, S., Gwilliam, R., Blackburn, H., Bumpstead, S. J., Dronov, S., Gillman, M., Gray, E., Hammond, N., Jayakumar, A., McCann, O. T., Liddle, J., Potter, S. C., Ravindrarajah, R., Ricketts, M., Tashakkori-Ghanbaria, A., Waller, M. J., Weston, P., Widaa, S., Whittaker, P., Barroso, I., Deloukas, P., McCarthy, M. I., Stefansson, K., Scolnick, E., Purcell, S., McCarroll, S. A., Sklar, P., Hultman, C. M., & Sullivan, P. F. (2013) Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nature Genetics, 45(10), pp. 1150-1159.
Fonte

Faculty of Health; Institute of Health and Biomedical Innovation
Palavras-Chave #cacna1a protein #cacna1c protein #cacnb2 protein #cacnb4 protein #calcium channel #calcium channel L type #calhm1 protein #calhm2 protein #calhm3 protein #cnnm2 protein #itih3 protein #itih4 protein #long untranslated RNA #matrix metalloproteinase 16 #polyadenylated RNA #sdccag8 protein #unclassified drug #wbp1l protein #adult #article #bipolar disorder #calcium signaling #chromosome 2 #controlled study #female #gene expression #gene locus #genetic analysis #genetic association #genetic risk #genetic variability #genotype #human #human genome #major clinical study #major histocompatibility complex #male #meta analysis (topic) #phenotype #priority journal #schizophrenia #single nucleotide polymorphism #Case-Control Studies #Genetic Predisposition to Disease #Genome-Wide Association Study #Humans #Polymorphism #Single Nucleotide #Sweden
Tipo

Journal Article
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