Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa
Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa
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DOI：
10.1016/j.cell.2019.10.004
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发表时间：
2019-10-31
期刊：
影响因子：
64.5
通讯作者：
Sandhu, Manj S.
中科院分区：
文献类型：
--
作者：
Gurdasani, Deepti;Carstensen, Tommy;Sandhu, Manj S.
非洲人群的基因组研究为了解疾病病因、人类多样性和人群历史提供了独特的机会。在同类最大的研究中，包括来自乌干达农村的6，400个个体的全基因组数据和1，978个个体的全基因组序列，我们发现了地理相关的精细规模人口亚结构的证据。从历史上看，现代乌干达人的祖先最能代表古代东非牧民的混合体。我们证明了价值最大的序列面板从非洲到目前为止作为一个插补资源。研究了34个心脏代谢性状，我们发现欧洲和非洲人群之间的性状遗传力存在系统性差异，这可能反映了基因和环境的差异影响。在一个多性状泛非洲GWAS多达14,126人，我们确定了新的基因座与人体测量，血液学，血脂和血糖性状。我们发现，几个功能上重要的信号是由非洲特有的变异驱动的，这突出了研究该地区不同人群的价值。
Genomic studies in African populations provide unique opportunities to understand disease etiology, human diversity, and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans was best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, hematological, lipid, and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.