A Bayesian genome screening of maximum number of drinks as an alcoholism phenotype with the new Haseman-Elston method

Abstract

Common human disorders, such as alcoholism, may be the result of interactions of many genes as well as environmental risk factors. Therefore, it is important to incorporate gene x gene and gene x environment interactions in complex disease gene mapping. In this study, we applied a robust Bayesian genome screening method that can incorporate interaction effects to map genes underlying alcoholism through its application to the data of the Collaborative Studies on Genetics of Alcoholism provided by Genetic Analysis Workshop 14. Our Bayesian genome screening method uses the regression-based stochastic variable selection, coupled with the new Haseman-Elston method to identify markers linked to phenotypes of interest. Compared to traditional linkage methods based on single-gene disease models, our method allows for multilocus disease models for simultaneous screening including both main and interaction (epistatic) effects. It is conceptually simple and computationally efficient through the use of Gibbs sampler. We conducted genome-wide analysis and comparison between scans based on microsatellites and singlenucleotide polymorphisms. A total of 328 microsatellites and 11,560 single-nucleotide polymorphisms (by Affymetrix) on 22 autosomal chromosomes and sex chromosome were used.