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

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posted on 27.08.2021, 12:40 by Fernanda S.G. Kehdy, Murilo Pita-Oliveira, Mariana M. Scudeler, Sabrina Torres-Loureiro, Camila Zolini, Rennan Moreira, Lucas A. Michelin, Isabela Alvim, Carolina Silva-Carvalho, Vinicius C. Furlan, Marla M. Aquino, Meddly L. Santolalla, Victor Borda, Giordano B. Soares-Souza, Luis Jaramillo-Valverde, Andres Vasquez-Dominguez, Cesar Sanchez Neira, Renato S. Aguiar, Ricardo A. Verdugo, Timothy D. O`Connor, Heinner Guio, Eduardo Tarazona-Santos, Thiago P. Leal, Fernanda Rodrigues-Soares

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.

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