McEvoy Brian P, Montgomery Grant W, McRae Allan F, Ripatti Samuli, Perola Markus, Spector Tim D, Cherkas Lynn, Ahmadi Kourosh R, Boomsma Dorret, Willemsen Gonneke, Hottenga Jouke J, Pedersen Nancy L, Magnusson Patrik K E, Kyvik Kirsten Ohm, Christensen Kaare, Kaprio Jaakko, Heikkilä Kauko, Palotie Aarno, Widen Elisabeth, Muilu Juha, Syvänen Ann-Christine, Liljedahl Ulrika, Hardiman Orla, Cronin Simon, Peltonen Leena, Martin Nicholas G, Visscher Peter M
Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Genome Res. 2009 May;19(5):804-14. doi: 10.1101/gr.083394.108. Epub 2009 Mar 5.
Population structure can provide novel insight into the human past, and recognizing and correcting for such stratification is a practical concern in gene mapping by many association methodologies. We investigate these patterns, primarily through principal component (PC) analysis of whole genome SNP polymorphism, in 2099 individuals from populations of Northern European origin (Ireland, United Kingdom, Netherlands, Denmark, Sweden, Finland, Australia, and HapMap European-American). The major trends (PC1 and PC2) demonstrate an ability to detect geographic substructure, even over a small area like the British Isles, and this information can then be applied to finely dissect the ancestry of the European-Australian and European-American samples. They simultaneously point to the importance of considering population stratification in what might be considered a small homogeneous region. There is evidence from F(ST)-based analysis of genic and nongenic SNPs that differential positive selection has operated across these populations despite their short divergence time and relatively similar geographic and environmental range. The pressure appears to have been focused on genes involved in immunity, perhaps reflecting response to infectious disease epidemic. Such an event may explain a striking selective sweep centered on the rs2508049-G allele, close to the HLA-G gene on chromosome 6. Evidence of the sweep extends over a 8-Mb/3.5-cM region. Overall, the results illustrate the power of dense genotype and sample data to explore regional population variation, the events that have crafted it, and their implications in both explaining disease prevalence and mapping these genes by association.
群体结构能够为人类历史提供全新的见解,并且在通过多种关联方法进行基因定位时,识别并校正这种分层现象是一个实际需要关注的问题。我们主要通过对来自北欧裔群体(爱尔兰、英国、荷兰、丹麦、瑞典、芬兰、澳大利亚以及国际人类基因组单体型图计划中的欧美裔群体)的2099名个体的全基因组单核苷酸多态性进行主成分(PC)分析,来研究这些模式。主要趋势(PC1和PC2)表明,即使在像不列颠群岛这样的小区域内,也能够检测到地理亚结构,然后可以利用这些信息来精细剖析欧洲裔澳大利亚人和欧美裔样本的祖先。它们同时指出了在一个可能被认为是小的同质区域内考虑群体分层的重要性。基于F(ST)对基因和非基因单核苷酸多态性的分析表明,尽管这些群体的分化时间较短且地理和环境范围相对相似,但不同的正向选择在这些群体中发挥了作用。这种压力似乎集中在与免疫相关的基因上,这可能反映了对传染病流行的反应。这样一个事件或许可以解释一个以rs2508049 - G等位基因为中心的显著选择性清除,该等位基因靠近6号染色体上的HLA - G基因。选择性清除的证据延伸到一个8兆碱基/3.5厘摩的区域。总体而言,这些结果说明了密集基因型和样本数据在探索区域群体变异、塑造这些变异的事件以及它们在解释疾病患病率和通过关联定位这些基因方面的作用。
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