Inferring Geographic Coordinates of Origin for Europeans Using Small Panels of Ancestry Informative Markers
Inferring Geographic Coordinates of Origin for Europeans Using Small Panels of Ancestry Informative Markers
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DOI：
10.1371/journal.pone.0011892
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发表时间：
2010-08-18
期刊：
影响因子：
3.7
通讯作者：
Paschou, Peristera
中科院分区：
文献类型：
--
作者：
Drineas, Petros;Lewis, Jamey;Paschou, Peristera
最近对欧洲人口的大规模研究表明，欧洲人口遗传结构的存在，以及使用来自数十万个遗传标记的信息来准确推断个体祖先的潜力。事实上，当欧洲人群的全基因组遗传变异被预测到二维主成分分析图时，一个令人惊讶的相关性与自我报告的祖先的实际地理坐标已经被报道。这种亚结构会阻碍对常见复杂疾病的易感基因的研究，从而导致虚假的相关性。因此，鉴定能够纠正种群分层的遗传标记变得至关重要。我们分析了来自11个种群的1200个个体超过50万个snp（种群参考样本）的基因分型，提出了一个系统的探索，在欧洲范围内，地理坐标的起源可以用小的snp面板来预测。如前所述，选择标记与数据集的顶部主成分相关联。通过彻底的交叉验证实验，我们表明，利用精心挑选的500或1000个snp的信息，在欧洲范围内，预测个体祖先的距离实际上只有几百公里是可能的。此外，我们表明这些面板可以用来正确地分配HapMap阶段3欧洲人口到他们的地理起源。我们提出的SNPs可以在各种不同的环境中被证明是非常有用的，例如分层校正或遗传血统测试，以及欧洲人口历史的研究。
Recent large-scale studies of European populations have demonstrated the existence of population genetic structure within Europe and the potential to accurately infer individual ancestry when information from hundreds of thousands of genetic markers is used. In fact, when genomewide genetic variation of European populations is projected down to a two-dimensional Principal Components Analysis plot, a surprising correlation with actual geographic coordinates of self-reported ancestry has been reported. This substructure can hamper the search of susceptibility genes for common complex disorders leading to spurious correlations. The identification of genetic markers that can correct for population stratification becomes therefore of paramount importance. Analyzing 1,200 individuals from 11 populations genotyped for more than 500,000 SNPs (Population Reference Sample), we present a systematic exploration of the extent to which geographic coordinates of origin within Europe can be predicted, with small panels of SNPs. Markers are selected to correlate with the top principal components of the dataset, as we have previously demonstrated. Performing thorough cross-validation experiments we show that it is indeed possible to predict individual ancestry within Europe down to a few hundred kilometers from actual individual origin, using information from carefully selected panels of 500 or 1,000 SNPs. Furthermore, we show that these panels can be used to correctly assign the HapMap Phase 3 European populations to their geographic origin. The SNPs that we propose can prove extremely useful in a variety of different settings, such as stratification correction or genetic ancestry testing, and the study of the history of European populations.