SEARCH

SEARCH BY CITATION

Keywords:

  • rheumatoid arthritis;
  • single-nucleotide polymorphisms;
  • multi-marker associations;
  • imputation;
  • population stratification;
  • gene-gene interactions;
  • biomarkers

Abstract

Genome-wide association studies of discrete traits generally use simple methods of analysis based on χ2 tests for contingency tables or logistic regression, at least for an initial scan of the entire genome. Nevertheless, more power might be obtained by using various methods that analyze multiple markers in combination. Methods based on sliding windows, wavelets, Bayesian shrinkage, or penalized likelihood methods, among others, were explored by various participants of Genetic Analysis Workshop 16 Group 1 to combine information across multiple markers within a region, while others used Bayesian variable selection methods for genome-wide multivariate analyses of all markers simultaneously. Imputation can be used to fill in missing markers on individual subjects within a study or in a meta-analysis of studies using different panels. Although multiple imputation theoretically should give more robust tests of association, one participant contribution found little difference between results of single and multiple imputation. Careful control of population stratification is essential, and two contributions found that previously reported associations with two genes disappeared after more precise control. Other issues considered by this group included subgroup analysis, gene-gene interactions, and the use of biomarkers. Genet. Epidemiol. 33 (Suppl. 1):S8–S12, 2009. © 2009 Wiley-Liss, Inc.