Bayesian logistic regression using a perfect phylogeny

Biostatistics. 2007 Jan;8(1):32-52. doi: 10.1093/biostatistics/kxj030. Epub 2006 Mar 23.

Abstract

Haplotype data capture the genetic variation among individuals in a population and among populations. An understanding of this variation and the ancestral history of haplotypes is important in genetic association studies of complex disease. We introduce a method for detecting associations between disease and haplotypes in a candidate gene region or candidate block with little or no recombination. A perfect phylogeny demonstrates the evolutionary relationship between single-nucleotide polymorphisms (SNPs) in the haplotype blocks. Our approach extends the logic regression technique of Ruczinski and others (2003) to a Bayesian framework, and constrains the model space to that of a perfect phylogeny. Environmental factors, as well as their interactions with SNPs, may be incorporated into the regression framework. We demonstrate our method on simulated data from a coalescent model, as well as data from a candidate gene study of sarcoidosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bayes Theorem*
  • Computer Simulation
  • Female
  • HLA-DQ Antigens / genetics
  • HLA-DQ beta-Chains
  • Haplotypes / genetics
  • Humans
  • Logistic Models*
  • Male
  • Models, Genetic*
  • Phylogeny*
  • Polymorphism, Single Nucleotide / genetics
  • Receptors, CCR2
  • Receptors, CCR5 / genetics
  • Receptors, Chemokine / genetics
  • Sarcoidosis / genetics
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • CCR2 protein, human
  • HLA-DQ Antigens
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • Receptors, CCR2
  • Receptors, CCR5
  • Receptors, Chemokine
  • Tumor Necrosis Factor-alpha