Population Structure of UK Biobank and Ancient Eurasians Reveals Adaptation at Genes Influencing Blood Pressure
Population Structure of UK Biobank and Ancient Eurasians Reveals Adaptation at Genes Influencing Blood Pressure
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DOI：
10.1016/j.ajhg.2016.09.014
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发表时间：
2016-11-03
影响因子：
9.8
通讯作者：
Price, Alkes L.
中科院分区：
文献类型：
--
作者：
Galinsky, Kevin J.;Loh, Po-Ru;Price, Alkes L.
分析密切相关群体之间的遗传差异可能是检测最近适应的有效方法。英国生物库的样本量非常大，非常适合于使用种群分化来检测选择，并能够以高分辨率分析英国种群结构。在这项研究中，对113,851个英国生物库样本的分析表明，英国的人口结构由五个主成分(PC)主导，横跨六个集群：北爱尔兰、苏格兰、英格兰北部、英格兰南部和两个威尔士集群。对古代欧亚人的分析表明，英国北部的人口具有更高的草原祖先水平，英国人口结构不能简单地解释为凯尔特人和撒克逊人的混合。对顶端PC异常群体分化的扫描发现，在FUT2的编码变体rs601338处存在全基因组显著的选择信号(p=9.16 x 10(-9))。此外，通过结合英国内部异常分化的证据和来自古代欧亚人的证据，我们识别了另外两个基因座最近选择的全基因组显著信号(p=5 x 10(-8))：CYP1A2-CSK和F12。我们在英国生物库中检测到舒张压与CYP1A2-CSK(p=1.10 x 10(-19))的选择信号变异体和ATXN2-SH2B3基因座(p=8.00 x 10(-33))的具有古代欧亚选择信号的变异体(p=8.00 x 10(-33))之间有很强的相关性，这意味着最近的适应与血压有关。
Analyzing genetic differences between closely related populations can be a powerful way to detect recent adaptation. The very large sample size of the UK Biobank is ideal for using population differentiation to detect selection and enables an analysis of the UK population structure at fine resolution. In this study, analyses of 113,851 UK Biobank samples showed that population structure in the UK is dominated by five principal components (PCs) spanning six clusters: Northern Ireland, Scotland, northern England, southern England, and two Welsh clusters. Analyses of ancient Eurasians revealed that populations in the northern UK have higher levels of Steppe ancestry and that UK population structure cannot be explained as a simple mixture of Celts and Saxons. A scan for unusual population differentiation along the top PCs identified a genome-wide-significant signal of selection at the coding variant rs601338 in FUT2 (p = 9.16 x 10(-9)). In addition, by combining evidence of unusual differentiation within the UK with evidence from ancient Eurasians, we identified genome-wide-significant (p = 5 x 10(-8)) signals of recent selection at two additional loci: CYP1A2-CSK and F12. We detected strong associations between diastolic blood pressure in the UK Biobank and both the variants with selection signals at CYP1A2-CSK (p = 1.10 x 10(-19)) and the variants with ancient Eurasian selection signals at the ATXN2-SH2B3 locus (p = 8.00 x 10(-33)), implicating recent adaptation related to blood pressure.