Gene ontology analysis of GWA study data sets provides insights into the biology of bipolar disorder.
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.
Holmans
Peter
P
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
EK
Pahwa
Jaspreet Singh
JS
Ferreira
Manuel A R
MA
Purcell
Shaun M
SM
Sklar
Pamela
P
Owen
Michael J
MJ
O'Donovan
Michael C
MC
Craddock
Nick
N
D001714:Bipolar Disorder / Q000235:genetics* / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods*; D003424:Crohn Disease / Q000235:genetics; D030541:Databases, Genetic; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide