A coordinate descent approach for sparse Bayesian learning in high dimensional QTL mapping and genome-wide association studies.

Abstract

Genomic scanning approaches that detect one locus at a time are subject to many problems in genome-wide association studies and quantitative trait locus mapping. The problems include large matrix inversion, over-conservativeness for tests after Bonferroni correction and difficulty in evaluation of the total genetic contribution to a trait's variance. Targeting these problems, we take a further step and investigate a multiple locus model that detects all markers simultaneously in a single model. We developed a sparse Bayesian learning (SBL) method for quantitative trait locus mapping and genome-wide association studies. This new method adopts a coordinate descent algorithm to estimate parameters (marker effects) by updating one parameter at a time conditional on current values of all other parameters. It uses an L2 type of penalty that allows the method to handle extremely large sample sizes (>100 000). Simulation studies show that SBL often has higher statistical powers and the simulated true loci are often detected with extremely small P-values, indicating that SBL is insensitive to stringent thresholds in significance testing. An R package (sbl) is available on the comprehensive R archive network (CRAN) and https://github.com/MeiyueComputBio/sbl/tree/master/R%20packge. Supplementary data are available at Bioinformatics online.