JSM 2004 - Toronto

Abstract #300756

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Activity Number: 72
Type: Topic Contributed
Date/Time: Monday, August 9, 2004 : 8:30 AM to 10:20 AM
Sponsor: Section on Statistics in Epidemiology
Abstract - #300756
Title: Estimating the Haplotype Specific Disease Risk in a Case-control Study
Author(s): E. S. Venkatraman*+ and Nandita Mitra and Colin B. Begg
Companies: Memorial Sloan-Kettering Cancer Center and Memorial Sloan-Kettering Cancer Center and Memorial Sloan-Kettering Cancer Center
Address: 1275 York Ave., New York, NY, 10021,
Keywords: haplotype ; case-control ; Hardy-Weinberg equilibrium
Abstract:

Estimation of the association between haplotypes and disease from a case-control study is considered. Assuming a single "disease haplotype" leads to increased risk, attention focusses on the relative risks associated with a single copy or two copies of the disease haplotype, relative to individuals with no copies. In this setting, case frequencies of the haplotype pairs are in Hardy- Weinberg Equilibrium (HWE) only if the influence of two copies of the disease haplotype on risk is multiplicative. Thus, imputation cannot rely on the assumption of HWE for cases. A method is presented for obtaining unbiased estimates of relative risks, making use of the EM algorithm and the assumption of HWE only for controls. The method accounts for the additional variation in the estimates due to the imputation of expected frequencies of haplotype pairs from ambiguous genotypes. A simulation study shows that the resulting confidence intervals have nominal coverage, and that the methods based on the assumption of HWE for both cases and controls can lead to bias.

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