Evaluation of logistic Bayesian LASSO for identifying association with rare haplotypes.

Abstract

It has been hypothesized that rare variants may hold the key to unraveling the genetic transmission mechanism of many common complex traits. Currently, there is a dearth of statistical methods that are powerful enough to detect association with rare haplotypes. One of the recently proposed methods is logistic Bayesian LASSO for case-control data. By penalizing the regression coefficients through appropriate priors, logistic Bayesian LASSO weeds out the unassociated haplotypes, making it possible for the associated rare haplotypes to be detected with higher powers. We used the Genetic Analysis Workshop 18 simulated data to evaluate the behavior of logistic Bayesian LASSO in terms of its power and type I error under a complex disease model. We obtained knowledge of the simulation model, including the locations of the functional variants, and we chose to focus on two genomic regions in the MAP4 gene on chromosome 3. The sample size was 142 individuals and there were 200 replicates.Despite the small sample size, logistic Bayesian LASSO showed high power to detect two haplotypes containing functional variants in these regions while maintaining low type I errors. At the same time, a commonly used approach for haplotype association implemented in the software hapassoc failed to converge because of the presence of rare haplotypes. Thus, we conclude that logistic Bayesian LASSO can play an important role in the search for rare haplotypes.