Gene Ontology Analysis of GWA Study Data Sets Provides Insights into the Biology of Bipolar Disorder
The American Journal of Human GeneticsPublished 19 June 2009Open access
Peter Holmans, Elaine Green, Jaspreet Singh Pahwa, Manuel A. R. Ferreira, Shaun Purcell, Pamela Sklar
Citations383
SJR quartileQ1
SJR score4.53
SNIP2.47
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TL;DR
The method, known as ALIGATOR (Association LIst Go AnnoTatOR), successfully detected biological pathways implicated in CD and implicated the modulation of transcription and cellular activity, including that which occurs via hormonal action, as an important player in pathogenesis.
Abstract
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.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
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