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PMID: 19539887 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

American journal of human genetics ·Vol. 85 ·No. 1 ·2009-07-00 ·Pages 13-24

Holmans P, Green EK, Pahwa JS, Ferreira MA, Purcell SM, Sklar P, Wellcome Trust Case-Control Consortium, Owen MJ, O'Donovan MC, Craddock N

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.

MeSH Terms
Bipolar Disorder/genetics,metabolism Computational Biology/methods Crohn Disease/genetics Databases, Genetic Genetic Predisposition to Disease Genome-Wide Association Study Humans Polymorphism, Single Nucleotide
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Holmans Peter
MRC Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Heath Park, CF23 6BQ Cardiff, UK. holmanspa@cardiff.ac.uk
Green Elaine K
Pahwa Jaspreet Singh
Ferreira Manuel A R
Purcell Shaun M
Sklar Pamela
Wellcome Trust Case-Control Consortium
Owen Michael J
O'Donovan Michael C
Craddock Nick
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
1537-6605
DOI
10.1016/j.ajhg.2009.05.011
Email
holmanspa@cardiff.ac.uk
Published
2009-07-00
Epub
2009-00-18
Pages
13-24
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC2706963
Subset
IM
Grants
Medical Research Council · G0801418 · United Kingdom
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1016/j.ajhg.2009.05.011 PMC Full Text View journal details
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