A cross-population extended haplotype-based homozygosity score test to detect positive selection in genome-wide scans.

In this article, we developed a cross-population comparison test statistic to detect chromosome regions in which there is no significant excess homozygosity in one population but homozygosity remains high in the other. We treated an extended stretch of homozygosity as a surrogate indicator of a recent positive selection. Conditioned on existing linkage disequilibrium, we proposed to test the haplotype version of the Hardy-Weinberg equilibrium (HWE). For each population, we assumed that a random sample of unrelated individuals were typed on a large number of single nucleotide polymorphisms (SNPs). A pooled-test statistic was constructed by comparing the measurements of homozygosity of the two samples around a core SNP. In the chromosome regions where HWE is roughly true in one population and HWE is not true in the other, the pooled-test statistic led to significant results to detect the positive selection. We evaluated the performance of the test statistic by type I error comparison and power evaluation. We showed that the proposed test statistic was very conservative and it had good power when the selected allele remains polymorphic. Then, we applied the test to HapMap Phase II data to make a comparison with previous results and to search for new candidate regions.