Journal Article

Genome-wide association analysis by lasso penalized logistic regression

Tong Tong Wu, Yi Fang Chen, Trevor Hastie, Eric Sobel and Kenneth Lange

in Bioinformatics

Volume 25, issue 6, pages 714-721
Published in print March 2009 | ISSN: 1367-4803
Published online January 2009 | e-ISSN: 1460-2059 | DOI: http://dx.doi.org/10.1093/bioinformatics/btp041
Genome-wide association analysis by lasso penalized logistic regression

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Motivation: In ordinary regression, imposition of a lasso penalty makes continuous model selection straightforward. Lasso penalized regression is particularly advantageous when the number of predictors far exceeds the number of observations.

Method: The present article evaluates the performance of lasso penalized logistic regression in case–control disease gene mapping with a large number of SNPs (single nucleotide polymorphisms) predictors. The strength of the lasso penalty can be tuned to select a predetermined number of the most relevant SNPs and other predictors. For a given value of the tuning constant, the penalized likelihood is quickly maximized by cyclic coordinate ascent. Once the most potent marginal predictors are identified, their two-way and higher order interactions can also be examined by lasso penalized logistic regression.

Results: This strategy is tested on both simulated and real data. Our findings on coeliac disease replicate the previous SNP results and shed light on possible interactions among the SNPs.

Availability: The software discussed is available in Mendel 9.0 at the UCLA Human Genetics web site.

Contact: klange@ucla.edu

Supplementary information: Supplementary data are available at Bioinformatics online.

Journal Article.  7050 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology

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