Gene ontology analysis of GWA study data sets provides insights into the biology of bipolar disorder - PubMed (original) (raw)
Gene ontology analysis of GWA study data sets provides insights into the biology of bipolar disorder
Peter Holmans et al. Am J Hum Genet. 2009 Jul.
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.
Figures
Figure 1
Flow Diagram Showing the Procedure for Estimating Statistical Significance
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