JSM 2005 - Toronto

Abstract #303811

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Legend: = Applied Session, = Theme Session, = Presenter
Activity Number: 385
Type: Topic Contributed
Date/Time: Wednesday, August 10, 2005 : 10:30 AM to 12:20 PM
Sponsor: Section on Statistical Consulting
Abstract - #303811
Title: Estimation of Genetic Effect at a Candidate Gene for Family-based Association Studies
Author(s): Mei-Chiung Shih*+ and Nan M. Laird and Christoph Lange
Companies: Harvard School of Public Health and Harvard School of Public Health and Harvard School of Public Health
Address: 655 Huntington Avenue, Boston, MA, 02115, United States
Keywords: TDT ; association test ; FBAT ; GEE ; retrospective likelihood ; relative risk
Abstract:

In contrast to the vast literature on testing genetic association, estimation of the genetic effect at a candidate gene is not as well-developed, except for the design of case-parents triads. Here, we present and compare two methods of estimating the relative risk parameters for data from general nuclear families. The first is based on maximizing the retrospective likelihood; the second is based on generalized estimating equations (GEE). Numerical studies demonstrate that when all parental genotypes are available or when the unobserved parental genotypes are correctly modeled, both methods yield consistent estimates of relative risks. When the unobserved parental genotypes are not modeled correctly, such as not incorporating population stratification and/or residual phenotypic correlation between siblings, the estimates given by the retrospective likelihood approach can be biased. In contrast, the GEE approach, by conditioning on the minimal sufficient statistics for the nuisance parameters involved in unobserved parental genotypes, still gives consistent estimates and is robust to population stratification. These methods are illustrated with a genetic study of asthma.

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