Application of sequential haplotype scan methods to case-control data

Haplotype association analysis based on arbitrarily chosen markers might lower statistical power because of the larger number of degrees of freedom caused by irrelevant makers. On the other hand, an exhaustive search for all possible combinations of markers for haplotype analysis is computationally expensive for genome-wide association analysis. To improve power, we applied our recently developed sequential haplotype scan method to case-control data for rheumatoid arthritis, including the PTPN22 candidate gene on chromosome 1p and the association mapping data on chromosome 18q, from the Genetic Analysis Workshop 15. The results showed that our new approach is at least as powerful as the traditional single-locus analysis and sometimes can be more powerful.