Gene Ontology Analysis of GWA Study Data Sets Provides Insights into the Biology of Bipolar Disorder

被引：318

作者：

Holmans, Peter ^{[1
]}

Green, Elaine K. ^{[1
]}

Pahwa, Jaspreet Singh ^{[1
]}

Ferreira, Manuel A. R. ^{[2
,3
,4
,5
,6
,7
]}

Purcell, Shaun M. ^{[2
,3
,4
,5
,6
]}

Sklar, Pamela ^{[2
,3
,4
,5
,6
]}

Owen, Michael J. ^{[1
]}

O'Donovan, Michael C. ^{[1
]}

Craddock, Nick ^{[1
]}

机构：

[1] Sch Med, Dept Psychol Med & Neurol, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF23 6BQ, S Glam, Wales

[2] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA

[3] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA

[4] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02114 USA

[5] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA

[6] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA

[7] Genet Epidemiol Queensland Inst Med Res, Brisbane, Qld 4029, Australia

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2009年 / 85卷 / 01期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; DISEASE; LINKS; PRIORITIZATION; SCHIZOPHRENIA; VARIANTS; PROTEIN; RISK; LOCI; AXIS;

D O I：

10.1016/j.ajhg.2009.05.011

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We present a method for testing overrepresentation of biological pathways, indexed by gene-ontology terms, in lists of significant SNPs from genome-wide association studies. This method corrects for linkage disequilibrium between SNPs, variable gene size, and multiple testing of nonindependent pathways. The method was applied to the Wellcome Trust Case-Control Consortium Crohn disease (CD) data set. At a general level, the biological basis of CD is relatively well known for a complex genetic trait, and it thus acted as a test of the method. The method, known as ALIGATOR (Association LIst Go AnnoTatOR), successfully detected biological pathways implicated in CD. The method was also applied to a meta-analysis of bipolar disorder, and it implicated the modulation of transcription and cellular activity, including that which occurs via hormonal action, as an important player in pathogenesis.

引用

页码：13 / 24

页数：12

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