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

全基因组关联研究 生物 精神分裂症(面向对象编程) 遗传关联 单核苷酸多态性 双相情感障碍 遗传学 候选基因 人口 精神科 基因 医学 神经科学 基因型 认知 环境卫生
作者
Stephan Ripke,Colm Ó'Dúshláine,Kimberly Chambert,Jennifer L. Moran,Anna K. Kähler,Susanne Akterin,Sarah E. Bergen,Ann L. Collins,James J. Crowley,Menachem Fromer,Yunjung Kim,Sang Lee,Patrik K. E. Magnusson,Nick Sanchez,Eli A. Stahl,Stephanie Williams,Naomi R. Wray,Kai Xia,Francesco Bettella,Anders D. Børglum,Brendan Bulik‐Sullivan,Paul Cormican,Nick Craddock,Christiaan de Leeuw,Naser Durmishi,Michael Gill,В. Е. Голимбет,Marian L. Hamshere,Peter Holmans,David M Hougaard,Kenneth S. Kendler,Kuang Lin,Derek W. Morris,Ole Mors,Preben Bo Mortensen,Benjamin M. Neale,F. Anthony O’Neill,Michael J. Owen,Miloš Milovančević,Daniëlle Posthuma,John Powell,Alexander Richards,Brien P. Riley,Douglas M. Ruderfer,Dan Rujescu,Engilbert Sigurðsson,Teimuraz Silagadze,August B. Smit,Hreinn Stefánsson,Stacy Steinberg,Jaana Suvisaari,Sarah Tosato,Matthijs Verhage,James Walters,Elvira Bramon,Aiden Corvin,Michael O’Donovan,Hreinn Stefánsson,Edward M. Scolnick,Shaun Purcell,Steven A. McCarroll,Pamela Sklar,Christina M. Hultman,Patrick F. Sullivan
出处
期刊:Nature Genetics [Springer Nature]
卷期号:45 (10): 1150-1159 被引量:1482
标识
DOI:10.1038/ng.2742
摘要

Patrick Sullivan and colleagues report a multi-stage genome-wide association study for schizophrenia in a Swedish population. They identify 13 loci newly associated with schizophrenia. 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.
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