Zhong Ming, Zhang Yiwei, Lange Kenneth, Fan Ruzong
Department of Statistics, The Texas A&M University, 447 Blocker Building, College Station, Texas 77843-3143, USA.
Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Stat Interface. 2011;4(1):51-63. doi: 10.4310/SII.2011.v4.n1.a6.
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.
在本文中，我们开发了一种跨群体比较检验统计量，以检测这样的染色体区域：在一个群体中不存在显著过量的纯合性，但在另一个群体中纯合性仍然很高。我们将一段延长的纯合性视为近期正选择的替代指标。基于现有的连锁不平衡，我们提议检验哈迪 - 温伯格平衡（HWE）的单倍型版本。对于每个群体，我们假设在大量单核苷酸多态性（SNP）上对无关个体的随机样本进行了分型。通过比较围绕一个核心SNP的两个样本的纯合性测量值，构建了一个合并检验统计量。在一个群体中HWE大致成立而在另一个群体中HWE不成立的染色体区域，合并检验统计量会得出显著结果以检测正选择。我们通过I型错误比较和效能评估来评估检验统计量的性能。我们表明，所提出的检验统计量非常保守，并且当所选等位基因保持多态性时具有良好的效能。然后，我们将该检验应用于HapMap二期数据，以便与先前的结果进行比较并寻找新的候选区域。
