Genome-wide association analysis by lasso penalized logistic regression

著者: Tong Tong Wu, Yi Fang Chen, Trevor Hastie, Eric M. Sobel, Kenneth Lange - Bioinformatics 2009 被引用: 831

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. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.