Evaluating haplotype effects in case-control studies via penalized-likelihood approaches: Prospective or retrospective analysis?

Abstract

Penalized likelihood methods have become increasingly popular in recent years for evaluating haplotype-phenotype association in case-control studies. Although a retrospective likelihood is dictated by the sampling scheme, these penalized methods are typically built on prospective likelihoods due to their modeling simplicity and computational feasibility. It has been well documented that for unpenalized methods, prospective analyses of case-control data can be valid but less efficient than their retrospective counterparts when testing for association, and result in substantial bias when estimating the haplotype effects. For penalized methods, which combine effect estimation and testing in one..