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Elastic-net regularization approaches for genome-wide association studies of rheumatoid arthritis

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Authors
Cho, Seoae; Kim, Haseong; Oh, Sohee; Kim, Kyunga; Park, Taesung
Issue Date
2009-12-15
Publisher
BioMed Central
Citation
BMC Proceedings, 3(Suppl 7):S25
Abstract
The current trend in genome-wide association studies is to identify regions where the true disease-causing genes may lie by evaluating thousands of single-nucleotide polymorphisms (SNPs) across the whole genome. However, many challenges exist in detecting disease-causing genes among the thousands of SNPs. Examples include multicollinearity and multiple testing issues, especially when a large number of correlated SNPs are simultaneously tested. Multicollinearity can often occur when predictor variables in a multiple regression model are highly correlated, and can cause imprecise estimation of association. In this study, we propose a simple stepwise procedure that identifies disease-causing SNPs simultaneously by employing elastic-net regularization, a variable selection method that allows one to address multicollinearity. At Step 1, the single-marker association analysis was conducted to screen SNPs. At Step 2, the multiple-marker association was scanned based on the elastic-net regularization. The proposed approach was applied to the rheumatoid arthritis (RA) case-control data set of Genetic Analysis Workshop 16. While the selected SNPs at the screening step are located mostly on chromosome 6, the elastic-net approach identified putative RA-related SNPs on other chromosomes in an increased proportion. For some of those putative RA-related SNPs, we identified the interactions with sex, a well known factor affecting RA susceptibility.
Language
English
URI
http://hdl.handle.net/10371/109988
DOI
https://doi.org/10.1186/1753-6561-3-S7-S25
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College of Natural Sciences (자연과학대학)Program in Bioinformatics (협동과정-생물정보학전공)Journal Papers (저널논문_협동과정-생물정보학전공)
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