title: A Monte Carlo test of linkage disequilibrium for single nucleotide polymorphisms.
abstract: BACKGROUND
  Genetic association studies, especially genome-wide studies, make use of linkage disequilibrium(LD) information between single nucleotide polymorphisms (SNPs). LD is also used for studying genome structure and has been valuable for evolutionary studies. The strength of LD is commonly measured by r2, a statistic closely related to the Pearson's χ2 statistic. However, the computation and testing of linkage disequilibrium using r2 requires known haplotype counts of the SNP pair, which can be a problem for most population-based studies where the haplotype phase is unknown. Most statistical genetic packages use likelihood-based methods to infer haplotypes. However, the variability of haplotype estimation needs to be accounted for in the test for linkage disequilibrium.
  
  
  RESULTS
  We develop a Monte Carlo based test for LD based on the null distribution of the r2 statistic. Our test is based on r2 and can be reported together with r2. Simulation studies show that it offers slightly better power than existing methods.
  
  
  CONCLUSIONS
  Our approach provides an alternative test for LD and has been implemented as a R program for ease of use. It also provides a general framework to account for other haplotype inference methods in LD testing.
authors.affiliation: Department of Biostatistics, Georgia Health Sciences University, Augusta,GA, USA. hxu@georgiahealth.edu.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Xu
authors.forename: Varghese
authors.initials: V
authors.lastname: George