在欧洲生物库中,祖先遗传成分与复杂的性状景观始终相关。

IF 3.7 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY European Journal of Human Genetics Pub Date : 2024-08-10 DOI:10.1038/s41431-024-01678-9
Vasili Pankratov, Massimo Mezzavilla, Serena Aneli, Ivan A. Kuznetsov, Daniela Fusco, James F. Wilson, Mait Metspalu, Paolo Provero, Luca Pagani, Davide Marnetto
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引用次数: 0

摘要

欧洲的遗传结构主要是由西部狩猎采集者、早期欧洲农民和草原青铜时代祖先之间的混杂形成的。这种结构被认为是全球基因组分析和后续研究中的混杂因素,目前已有金标准方法对其进行校正。然而,人们对这些祖先成分在多大程度上促成了当今欧洲的复杂性状变异仍然知之甚少。在这项研究中,我们利用英国生物库来解决这个问题。通过广泛的人口模拟,利用兄弟姐妹的数据,并结合我们之前从爱沙尼亚生物库中获得的结果,我们仔细评估了我们发现的意义和范围。心率、血小板计数、骨矿物质密度和许多其他特征显示出与身高和色素特征类似的分层现象,很可能是祖先群体间选择和分化的目标。我们利用同胞之间的祖先差异证实了我们的结果,从而表明所报告的祖先与性状之间的关联并非由环境干扰因素驱动。我们在不同生物库中得出的结果的一致性进一步证明了这一点,并表明这些源自新石器时代后混血事件的遗传倾向是变异性的来源,也是整个欧洲的潜在混杂因素。
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Ancestral genetic components are consistently associated with the complex trait landscape in European biobanks
The genetic structure in Europe was mostly shaped by admixture between the Western Hunter-Gatherers, Early European Farmers and Steppe Bronze Age ancestral components. Such structure is regarded as a confounder in GWAS and follow-up studies, and gold-standard methods exist to correct for it. However, it is still poorly understood to which extent these ancestral components contribute to complex trait variation in present-day Europe. In this work we harness the UK Biobank to address this question. By extensive demographic simulations, exploiting data on siblings and incorporating previous results we obtained from the Estonian Biobank, we carefully evaluate the significance and scope of our findings. Heart rate, platelet count, bone mineral density and many other traits show stratification similar to height and pigmentation traits, likely targets of selection and divergence across ancestral groups. We show that the reported ancestry-trait associations are not driven by environmental confounders by confirming our results when using between-sibling differences in ancestry. The consistency of our results across biobanks further supports this and indicates that these genetic predispositions that derive from post-Neolithic admixture events act as a source of variability and as potential confounders in Europe as a whole.
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来源期刊
European Journal of Human Genetics
European Journal of Human Genetics 生物-生化与分子生物学
CiteScore
9.90
自引率
5.80%
发文量
216
审稿时长
2 months
期刊介绍: The European Journal of Human Genetics is the official journal of the European Society of Human Genetics, publishing high-quality, original research papers, short reports and reviews in the rapidly expanding field of human genetics and genomics. It covers molecular, clinical and cytogenetics, interfacing between advanced biomedical research and the clinician, and bridging the great diversity of facilities, resources and viewpoints in the genetics community. Key areas include: -Monogenic and multifactorial disorders -Development and malformation -Hereditary cancer -Medical Genomics -Gene mapping and functional studies -Genotype-phenotype correlations -Genetic variation and genome diversity -Statistical and computational genetics -Bioinformatics -Advances in diagnostics -Therapy and prevention -Animal models -Genetic services -Community genetics
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