Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs

被引：425

作者：

Lee, S. Hong ^{[1
,2
]}

DeCandia, Teresa R. ^{[3
,4
]}

Ripke, Stephan ^{[5
,6
,7
]}

Yang, Jian ^{[2
,8
]}

Sullivan, Patrick F. ^{[9
]}

Goddard, Michael E. ^{[10
,11
]}

Keller, Matthew C. ^{[3
,4
]}

Visscher, Peter M. ^{[1
,2
,8
]}

Wray, Naomi R. ^{[1
,2
]}

机构：

[1] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia

[2] Queensland Inst Med Res, Brisbane, Qld 4006, Australia

[3] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA

[4] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA

[5] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA

[6] MIT, Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA 02139 USA

[7] Harvard Univ, Cambridge, MA 02138 USA

[8] Univ Queensland, Princess Alexandra Hosp, Diamantina Inst, Brisbane, Qld 4102, Australia

[9] Univ N Carolina, Dept Genet, Chapel Hill, NC USA

[10] Univ Melbourne, Dept Agr & Food Syst, Melbourne, Vic, Australia

[11] Dept Primary Ind, Biosci Res Div, Melbourne, Vic, Australia

来源：

NATURE GENETICS | 2012年 / 44卷 / 03期

基金：

澳大利亚研究理事会; 英国医学研究理事会;

关键词：

VARIANTS; DISEASE; TRAIT;

D O I：

10.1038/ng.1108

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Schizophrenia is a complex disorder caused by both genetic and environmental factors. Using 9,087 affected individuals, 12,171 controls and 915,354 imputed SNPs from the Schizophrenia Psychiatric Genome-Wide Association Study (GWAS) Consortium (PGC-SCZ), we estimate that 23% (s.e. = 1%) of variation in liability to schizophrenia is captured by SNPs. We show that a substantial proportion of this variation must be the result of common causal variants, that the variance explained by each chromosome is linearly related to its length (r = 0.89, P = 2.6 x 10(-8)), that the genetic basis of schizophrenia is the same in males and females, and that a disproportionate proportion of variation is attributable to a set of 2,725 genes expressed in the central nervous system (CNS; P = 7.6 x 10(-8)). These results are consistent with a polygenic genetic architecture and imply more individual SNP associations will be detected for this disease as sample size increases.

引用

页码：247 / U35

页数：6

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