Department of Statistics Seminar
North Carolina State University

presents

Dr. Danyu Lin

University of North Carolina

"Likelihood-Based Inference on Haplotype Effects in Genetic Association Studies"

ABSTRACT

Haplotype is a specific sequence of nucleotides on a single chromosome. The population associations between haplotypes and disease phenotypes provide critical information about the genetic basis of complex human diseases. Standard genotyping techniques cannot distinguish the two homologous chromosomes of an individual so that only the unphased genotype (i.e., the combination of the two homologous haplotypes) is directly observable. Statistical inference about haplotype-phenotype associations based on unphased genotype data presents a very interesting and difficult missing-data problem, especially when the sampling depends on the disease status. The objective of the present work is to provide a comprehensive and rigorous treatment of this problem. All commonly used study designs, including prospective, case-control and cohort studies, are considered. The phenotype can be a disease indicator, a quantitative trait or a potentially censored time to disease variable. The effects of haplotypes on the phenotype are formulated through flexible regression models, which can accommodate a variety of genetic mechanisms and gene-environment interactions. Appropriate likelihoods are constructed under mild conditions allowing Hardy-Weinberg disequilibrium. The identifiability of the parameters, and the consistency, asymptotic normality and efficiency of the maximum likelihood estimators are established. Efficient and reliable numerical algorithms are developed. Simulation studies show that the likelihood-based procedures perform well in practical settings. Application to the Finland-United States Investigation of NIDDM Genetics Study is provided. Areas in need of further development are discussed.

Friday, April, 16, 2004

3:35 - 4:35 pm

206 Cox Hall

Refreshments will be served on the second floor of Dabney Hall (left of Room 222) at 3:00 pm.