Human-SARS-CoV-2 interactome and human genetic diversity: TMPRSS2-rs2070788, associated with severe influenza, and its population genetics caveats in Native Americans

Abstract For human/SARS-CoV-2 interactome genes ACE2, TMPRSS2 and BSG, there is a convincing evidence of association in Asians with influenza-induced SARS for TMPRSS2-rs2070788, tag-SNP of the eQTL rs383510. This case illustrates the importance of population genetics and of sequencing data in the design of genetic association studies in different human populations: the high linkage disequilibrium (LD) between rs2070788 and rs383510 is Asian-specific. Leveraging on a combination of genotyping and sequencing data for Native Americans (neglected in genetic studies), we show that while their frequencies of the Asian tag-SNP rs2070788 is, surprisingly, the highest worldwide, it is not in LD with the eQTL rs383510, that therefore, should be directly genotyped in genetic association studies of SARS in populations with Native American ancestry.

针对人类与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的互作组基因ACE2、TMPRSS2及BSG，已有确凿证据表明，在亚洲人群中，TMPRSS2基因的rs2070788（即表达数量性状位点（expression quantitative trait locus, eQTL）rs383510的标签单核苷酸多态性（tag-SNP））与流感诱发的重症急性呼吸综合征（Severe Acute Respiratory Syndrome, SARS）存在关联。该案例凸显了人群遗传学及测序数据在不同人群遗传关联研究设计中的重要性：rs2070788与rs383510之间的高连锁不平衡（linkage disequilibrium, LD）仅为亚洲人群所特有。本研究结合基因分型与测序数据，对此前被遗传研究忽视的美洲原住民人群展开分析，结果令人意外地发现，该人群中亚洲来源的标签SNP rs2070788的频率为全球最高，但该位点与eQTL rs383510之间并不存在连锁不平衡，因此在针对美洲原住民血统人群的SARS遗传关联研究中，应直接对rs383510位点进行基因分型检测。