Portal de Periódicos da CAPES

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

2009; Elsevier BV; Volume: 85; Issue: 1 Linguagem: Inglês

10.1016/j.ajhg.2009.05.011

1537-6605

Peter Holmans, Elaine Green, Jaspreet Singh Pahwa, Manuel A. R. Ferreira, Shaun Purcell, Pamela Sklar, Michael J. Owen, Michael O’Donovan, Nick Craddock,

Inflammatory Bowel Disease

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.