Locating disease genes using Bayesian variable selection with the Haseman-Elston method

BMC Genet. 2003 Dec 31;4 Suppl 1(Suppl 1):S69. doi: 10.1186/1471-2156-4-S1-S69.

Abstract

Background: We applied stochastic search variable selection (SSVS), a Bayesian model selection method, to the simulated data of Genetic Analysis Workshop 13. We used SSVS with the revisited Haseman-Elston method to find the markers linked to the loci determining change in cholesterol over time. To study gene-gene interaction (epistasis) and gene-environment interaction, we adopted prior structures, which incorporate the relationship among the predictors. This allows SSVS to search in the model space more efficiently and avoid the less likely models.

Results: In applying SSVS, instead of looking at the posterior distribution of each of the candidate models, which is sensitive to the setting of the prior, we ranked the candidate variables (markers) according to their marginal posterior probability, which was shown to be more robust to the prior. Compared with traditional methods that consider one marker at a time, our method considers all markers simultaneously and obtains more favorable results.

Conclusions: We showed that SSVS is a powerful method for identifying linked markers using the Haseman-Elston method, even for weak effects. SSVS is very effective because it does a smart search over the entire model space.

MeSH terms

  • Bayes Theorem
  • Chromosome Mapping / statistics & numerical data*
  • Computer Simulation / statistics & numerical data
  • Epistasis, Genetic
  • Female
  • Genetic Linkage*
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Least-Squares Analysis
  • Male
  • Matched-Pair Analysis
  • Models, Genetic
  • Quantitative Trait Loci / genetics*
  • Quantitative Trait, Heritable
  • Siblings
  • Stochastic Processes
  • Time

Substances

  • Genetic Markers