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Gene ontology analysis of GWA study data sets provides insights into the biology of bipolar disorder

Holmans, Peter Alan, Green, Elaine Karen, Pahwa, Jaspreet Singh, Ferreira, Manuel A.R., Purcell, Shaun M., Sklar, Pamela, The Wellcome Trust Case-Control Consortium, , Owen, Michael John, O'Donovan, Michael Conlon and Craddock, Nicholas Johon 2009. Gene ontology analysis of GWA study data sets provides insights into the biology of bipolar disorder. American Journal of Human Genetics 85 (1) , pp. 13-24. 10.1016/j.ajhg.2009.05.011

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Medicine
Systems Immunity Research Institute (SIURI)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
Publisher: Elsevier
ISSN: 0002-9297
Last Modified: 02 May 2019 12:33
URI: http://orca.cf.ac.uk/id/eprint/23728

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