Bayesian analysis of multilocus association in quantitative and qualitative traits.

Abstract

A Bayesian model-based method for multilocus association analysis of quantitative and qualitative (binary) traits is presented. The method selects a trait-associated subset of markers among candidates, and is equally applicable for analyzing wide chromosomal segments (genome scans) and small candidate regions. The method can be applied in situations involving missing genotype data. The number of trait loci, their marker positions, and the magnitudes of their gene effects (strengths of association) are all estimated simultaneously. The inference of parameters is based on their posterior distributions, which are obtained through Markov chain Monte Carlo simulations. The strengths of the approach are: 1) flexible use of oligogenic models with unknown number of loci, 2) performing the estimation of association jointly with model selection, and 3) avoidance of the multiple testing problem, which typically complicates the approaches based on association testing. The performance of the method was tested and compared to the multilocus conditional search procedure by analyzing two simulated data sets. We also applied the method to cystic fibrosis haplotype data (two-locus haplotypes), where gene position has already been identified. The method is implemented as a software package, which is freely available for research purposes under the name BAMA.