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

Holmans, Peter Alan ORCID: https://orcid.org/0000-0003-0870-9412, Green, Elaine Karen, Pahwa, Jaspreet Singh, Ferreira, Manuel A.R., Purcell, Shaun M., Sklar, Pamela, The Wellcome Trust Case-Control Consortium, Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862, O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379 and Craddock, Nicholas Johon ORCID: https://orcid.org/0000-0003-2171-0610 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:	19 Oct 2022 10:15
URI:	https://orca.cardiff.ac.uk/id/eprint/23728

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