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Gene Ontology Analysis of GWA Study Data Sets Provides Insights into the Biology of Bipolar Disorder
Open accessAbstract
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.
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“Analyses of bipolar disorder provided evidence of association with hormone action and adherens junctions7,9,10”
From Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways (2015) · cites this paper as [9]
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“INRICH45, ALIGATOR9 and MAGENTA46 are “best SNP per gene” methods that count the number of genes in a pathway where a number of independent SNPs exceed a predefined significance, and adjust for LD and genomic structure with corrected statistics derived by Monte-Carlo simulation.”
From Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways (2015) · cites this paper as [9]
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Metadata
- Authors
- Holmans, P., Green, E. K., Pahwa, J. S., Ferreira, M. A. R., Purcell, S. M., Sklar, P., Owen, M. J., O'Donovan, M. C., & Craddock, N.
- Affiliations
- Cardiff University (GB)
- Broad Institute (US)
- Corresponding author
- Holmans, Peter
- ORCID
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2009-07
- Volume
- 85
- Issue
- 1
- Pages
- 13-24
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC2706963
- OpenAlex
- W1991160835
- Cited by
- 378
- References
- 45
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 8 · 2022: 4 · 2021: 12 · 2020: 19 · 2019: 16 · 2018: 18 · 2017: 17 · 2016: 28 · 2015: 34 · 2014: 34 · 2013: 38 · 2012: 52
- FWCI
- 19.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Health Informatics › Biomedical Text Mining and Ontologies
- Keywords
- Gene Ontology, genome-wide association study, single nucleotide polymorphisms, multiple testing correction, Crohn's disease, bipolar disorder, transcriptional regulation, hormone signaling, pathogenesis
- MeSH terms
- Bipolar Disorder, Crohn Disease, Humans, Computational Biology, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Databases, Genetic, Genome-Wide Association Study
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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