Statistical tests for admixture mapping with case-control and cases-only data
Statistical tests for admixture mapping with case-control and cases-only data
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DOI：
10.1086/425281
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发表时间：
2004-11-01
影响因子：
9.8
通讯作者：
Pritchard, JK
中科院分区：
文献类型：
--
作者：
Montana, G;Pritchard, JK
混合作图是一种很有前途的新工具，发现基因，有助于复杂的性状。这种作图方法使用来自最近混合的人群的样本来检测易感基因座，在该易感基因座处，风险等位基因在原始贡献人群中具有不同的频率。虽然混合作图的想法已经存在了十多年，但基因组工具现在才变得可用，使其成为复杂性状作图的可行和有吸引力的选择。在这篇文章中，我们描述了新的统计方法，用于分析混合映射研究的多点数据，以检测“祖先关联”。“新的测试统计数据并没有假设特定的疾病模型;相反，它们只是基于样本在某个位点的祖先比例偏离基因组平均值的程度。我们的功率计算表明，对于潜在的风险等位基因频率在祖先人群中有很大差异的基因座，混合映射的功率可以与关联映射相媲美，但标记的数量要少得多。我们还表明，虽然“祖先信息标记”（AIM）是上级随机单核苷酸多态性（SNP），随机SNP可以表现得很好，当AIM不可用。因此，研究混合人群的研究人员，AIM是不可用的，可以执行混合映射与使用适度更高密度的随机标记。执行基因图谱计算的软件“MALDsoft”可在Pritchard实验室网站上免费获得。
Admixture mapping is a promising new tool for discovering genes that contribute to complex traits. This mapping approach uses samples from recently admixed populations to detect susceptibility loci at which the risk alleles have different frequencies in the original contributing populations. Although the idea for admixture mapping has been around for more than a decade, the genomic tools are only now becoming available to make this a feasible and attractive option for complex-trait mapping. In this article, we describe new statistical methods for analyzing multipoint data from admixture-mapping studies to detect "ancestry association." The new test statistics do not assume a particular disease model; instead, they are based simply on the extent to which the sample's ancestry proportions at a locus deviate from the genome average. Our power calculations show that, for loci at which the underlying risk-allele frequencies are substantially different in the ancestral populations, the power of admixture mapping can be comparable to that of association mapping but with a far smaller number of markers. We also show that, although "ancestry informative markers" (AIMs) are superior to random single-nucleotide polymorphisms ( SNPs), random SNPs can perform quite well when AIMs are not available. Hence, researchers who study admixed populations in which AIMs are not available can perform admixture mapping with the use of modestly higher densities of random markers. Software to perform the gene-mapping calculations, "MALDsoft," is freely available on the Pritchard Lab Web site.