American Statistical Association
New York City
Metropolitan Area Chapter

Mailman School of Public Health
Columbia University
Department of Biostatistics Colloquium



ESTIMATION OF GENOTYPE RELATIVE RISKS
FROM PEDIGREE DATA BY COMPOSITE LIKELIHOODS

by

Prof. Daniel Schaid
Department of Biostatistics
Mayo Clinic


Abstract

Recent genome wide association studies based on large case-control samples suggest that multiple single nucleotide polymorphsims (SNPs) are associated with prostate cancer, with odds ratios on the order of 1.2 - 1.5. This low level of risk is difficult to detect in traditional family-based linkage studies, but large collections of families are available to evaluate whether the risks observed in large case-control studies are relevant to pedigrees. However, pedigrees selected for linkage studies are highly ascertained for many affected members, making it difficult to precisely define the sampling scheme. This makes it nearly impossible to correct for pedigree ascertainment. As an alternative, we consider a conditional "retrospective" likelihood for the distribution of genotypes in pedigrees, conditional on pedigree members being affected with disease. This likelihood, joint for all affected pedigree members, depends on a genotype relative risk parameter, and population allele frequencies. The computational burden to evaluate this joint conditional likelihood can be dramatically reduced by focusing on the marginal likelihood for pairs of subjects. By combining all possible pairs of marginal likelihoods, a composite likelihood is computationally feasible. This composite likelihood will be used to compute genotype relative risks for pedigrees with prostate cancer, and compared to odds ratios computed from case-control studies. The statistical efficiency and potential bias of the composite likelihood method will be discussed.


Date: Thursday, January 22, 2009
Time: 4:00 - 5:00 P.M.
Location: Mailman School of Public Health
Department of Biostatistics
722 West 168th Street
Biostatistics Computer Lab
6th Floor - Room 656
New York, New York

RESERVATIONS ARE NOT REQUIRED

Refreshments will be served at 3:30 P.M. in the
Biostatistics Conference Room (R627).


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