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Using Prior Information from the Medical Literature in GWAS of Oral Cancer Identifies Novel Susceptibility Variant on Chromosome 4-the AdAPT Method

Lookup NU author(s): Professor Peter Thomson

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Abstract

Background: Genome-wide association studies (GWAS) require large sample sizes to obtain adequate statistical power, but it may be possible to increase the power by incorporating complementary data. In this study we investigated the feasibility of automatically retrieving information from the medical literature and leveraging this information in GWAS. Methods: We developed a method that searches through PubMed abstracts for pre-assigned keywords and key concepts, and uses this information to assign prior probabilities of association for each single nucleotide polymorphism (SNP) with the phenotype of interest - the Adjusting Association Priors with Text (AdAPT) method. Association results from a GWAS can subsequently be ranked in the context of these priors using the Bayes False Discovery Probability (BFDP) framework. We initially tested AdAPT by comparing rankings of known susceptibility alleles in a previous lung cancer GWAS, and subsequently applied it in a two-phase GWAS of oral cancer. Results: Known lung cancer susceptibility SNPs were consistently ranked higher by AdAPT BFDPs than by p-values. In the oral cancer GWAS, we sought to replicate the top five SNPs as ranked by AdAPT BFDPs, of which rs991316, located in the ADH gene region of 4q23, displayed a statistically significant association with oral cancer risk in the replication phase (per-rare-allele log additive p-value [p(trend)] = 2.5 x 10(-3)). The combined OR for having one additional rare allele was 0.83 (95% CI: 0.76-0.90), and this association was independent of previously identified susceptibility SNPs that are associated with overall UADT cancer in this gene region. We also investigated if rs991316 was associated with other cancers of the upper aerodigestive tract (UADT), but no additional association signal was found. Conclusion: This study highlights the potential utility of systematically incorporating prior knowledge from the medical literature in genome-wide analyses using the AdAPT methodology. AdAPT is available online (url: http://services.gate.ac.uk/lld/gwas/service/config).


Publication metadata

Author(s): Johansson M, Roberts A, Chen D, Li YY, Delahaye-Sourdeix M, Aswani N, Greenwood MA, Benhamou S, Lagiou P, Holcatova I, Richiardi L, Kjaerheim K, Agudo A, Castellsague X, Macfarlane TV, Barzan L, Canova C, Thakker NS, Conway DI, Znaor A, Healy CM, Ahrens W, Zaridze D, Szeszenia-Dabrowska N, Lissowska J, Fabianova E, Mates IN, Bencko V, Foretova L, Janout V, Curado MP, Koifman S, Menezes A, Wunsch V, Eluf-Neto J, Boffetta P, Franceschi S, Herrero R, Garrote LF, Talamini R, Boccia S, Galan P, Vatten L, Thomson P, Zelenika D, Lathrop M, Byrnes G, Cunningham H, Brennan P, Wakefield J, Mckay JD

Publication type: Article

Publication status: Published

Journal: PLoS One

Year: 2012

Volume: 7

Issue: 5

Print publication date: 01/05/2012

Date deposited: 15/08/2012

ISSN (electronic): 1932-6203

Publisher: Public Library of Science

URL: http://dx.doi.org/10.1371/journal.pone.0036888

DOI: 10.1371/journal.pone.0036888


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Funding

Funder referenceFunder name
EU
INCa (Institut National du Cancer, France)
1R03DE020116National Institute of Dental and Craniofacial Research
FP7-215535
R01 CA092039 05United States National Cancer Institute

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