Incorporating prior biologic information for high-dimensional rare variant association studies Journal Article


Authors: Quintana, M. A.; Schumacher, F. R.; Casey, G.; Bernstein, J. L.; Li, L.; Conti, D. V.
Article Title: Incorporating prior biologic information for high-dimensional rare variant association studies
Abstract: Background: Given the increasing scale of rare variant association studies, we introduce a method for high-dimensional studies that integrates multiple sources of data as well as allows for multiple region-specific risk indices. Methods: Our method builds upon the previous Bayesian risk index by integrating external biological variant-specific covariates to help guide the selection of associated variants and regions. Our extension also incorporates a second level of uncertainty as to which regions are associated with the outcome of interest. Results: Using a set of study-based simulations, we show that our approach leads to an increase in power to detect true associations in comparison to several commonly used alternatives. Additionally, the method provides multi-level inference at the pathway, region and variant levels. Conclusion: To demonstrate the flexibility of the method to incorporate various types of information and the applicability to high-dimensional data, we apply our method to a single region within a candidate gene study of second primary breast cancer and to multiple regions within a candidate pathway study of colon cancer. Copyright © 2013 S. Karger AG, Basel.
Keywords: sequence analysis; dna repair; genetic predisposition to disease; breast cancer; bayes theorem; analytic method; colonic neoplasms; genetic association; genetic variability; genetic variation; breast neoplasms; brca1 protein; mathematical model; simulation; models, statistical; colon cancer; models, genetic; computer simulation; rare disease; bayes factors; bayesian model uncertainty; genetic association studies; rare variant analysis; bayesian risk index
Journal Title: Human Heredity
Volume: 74
Issue: 3-4
ISSN: 0001-5652
Publisher: S. Karger AG  
Date Published: 2012-01-01
Start Page: 184
End Page: 195
Language: English
PROVIDER: scopus
PUBMED: 23594496
DOI: 10.1159/000346021
PMCID: PMC4058572
DOI/URL:
Notes: --- - Cited By (since 1996):1 - "Export Date: 1 May 2013" - "CODEN: HUHEA" - ":doi 10.1159/000346021" - "Source: Scopus"
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  1. Jonine L Bernstein
    142 Bernstein