Optimal Step Length EM Algorithm (OSLEM) for the estimation of haplotype frequency and its application in lipoprotein lipase genotyping

BACKGROUND: Haplotype based linkage disequilibrium (LD) mapping has become a powerful and cost-effective method for performing genetic association studies, particularly in the search for genetic markers in linkage disequilibrium with complex disease loci. Various methods (e.g. Monte-Carlo (Gibbs sampling); EM (expectation maximization); and Clark's method) have been used to estimate haplotype frequencies from routine genotyping data. RESULTS: These algorithms can be very slow for large number of SNPs. In order to speed them up, we have developed a new algorithm using numerical analysis technology, a so-called optimal step length EM (OSLEM) that accelerates the calculation. By optimizing approximately the step length of the EM algorithm, OSLEM can run at about twice the speed of EM. This algorithm has been used for lipoprotein lipase (LPL) genotyping analysis. CONCLUSIONS: This new optimal step length EM (OSLEM) algorithm can accelerate the calculation for haplotype frequency estimation for genotyping data without pedigree information. An OSLEM on-line server is available, as well as a free downloadable version.