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    Am J Hum Genet. 2009 Jul;85(1):13-24. doi: 10.1016/j.ajhg.2009.05.011. Epub 2009 Jun 18.

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

    Source

    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

    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.

    PMID:
    19539887
    [PubMed - indexed for MEDLINE]
    PMCID:
    PMC2706963
    Free PMC Article

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