Estimating haplotype relative risks on human survival in population-based association studies.

Published

Journal Article

Association-based linkage disequilibrium (LD) mapping is an increasingly important tool for localizing genes that show potential influence on human aging and longevity. As haplotypes contain more LD information than single markers, a haplotype-based LD approach can have increased power in detecting associations as well as increased robustness in statistical testing. In this paper, we develop a new statistical model to estimate haplotype relative risks (HRRs) on human survival using unphased multilocus genotype data from unrelated individuals in cross-sectional studies. Based on the proportional hazard assumption, the model can estimate haplotype risk and frequency parameters, incorporate observed covariates, assess interactions between haplotypes and the covariates, and investigate the modes of gene function. By introducing population survival information available from population statistics, we are able to develop a procedure that carries out the parameter estimation using a nonparametric baseline hazard function and estimates sex-specific HRRs to infer gene-sex interaction. We also evaluate the haplotype effects on human survival while taking into account individual heterogeneity in the unobserved genetic and nongenetic factors or frailty by introducing the gamma-distributed frailty into the survival function. After model validation by computer simulation, we apply our method to an empirical data set to measure haplotype effects on human survival and to estimate haplotype frequencies at birth and over the observed ages. Results from both simulation and model application indicate that our survival analysis model is an efficient method for inferring haplotype effects on human survival in population-based association studies.

Full Text

Duke Authors

Cited Authors

  • Tan, Q; Christiansen, L; Bathum, L; Zhao, JH; Yashin, AI; Vaupel, JW; Christensen, K; Kruse, TA

Published Date

  • January 2005

Published In

Volume / Issue

  • 59 / 2

Start / End Page

  • 88 - 97

PubMed ID

  • 15838178

Pubmed Central ID

  • 15838178

Electronic International Standard Serial Number (EISSN)

  • 1423-0062

International Standard Serial Number (ISSN)

  • 0001-5652

Digital Object Identifier (DOI)

  • 10.1159/000085223

Language

  • eng