Abstract

Typically locus specific genotype data do not contain information regarding the gametic phase of haplotypes, especially when an individual is heterozygous at more than one locus among a large number of linked polymorphic loci. Thus, studying disease-haplotype association using unphased genotype data is essentially a problem of handling a missing covariate in a case-control design. There are several methods for estimating a disease-haplotype association parameter in a matched case-control study. Here we propose a conditional likelihood approach for inference regarding the disease-haplotype association using unphased genotype data arising from a matched case-control study design. The proposed method relies on a logistic disease risk model and a Hardy-Weinberg equilibrium (HWE) among the control population only. We develop an expectation and conditional maximization (ECM) algorithm for jointly estimating the haplotype frequency and the disease-haplotype association parameter(s). We apply the proposed method to analyze the data from the Alpha-Tocopherol, Beta-Carotene Cancer prevention study, and a matched case-control study of breast cancer patients conducted in Israel. The performance of the proposed method is evaluated via simulation studies.

Recommended Citation

Sinha, Samiran; Gruber, Stephen B.; Mukherjee, Bhramar; and Rennert, Gad (2008) "Inference of the Haplotype Effect in a Matched Case-Control Study Using Unphased Genotype Data," The International Journal of Biostatistics: Vol. 4 : Iss. 1, Article 6.
Available at: http://www.bepress.com/ijb/vol4/iss1/6