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\begin{document}

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



\author[1]{Fernanda Kehdy}%
\author[2]{Murilo Pita-Oliveira}%
\author[2]{Mariana Scudeler}%
\author[2]{Sabrina Torres-Loureiro}%
\author[3]{Camila Zolini}%
\author[3]{Rennan Moreira}%
\author[3]{Lucas Michelin}%
\author[3]{Isabela Alvim}%
\author[3]{Carolina Silva-Carvalho}%
\author[3]{Vinicius Furlan}%
\author[3]{Marla Aquino}%
\author[4]{Meddly Santollala}%
\author[5]{Victor Borda}%
\author[3]{Giordano Soares-Souza}%
\author[6]{Luis Jaramillo-Valverde}%
\author[6]{Andres Vasquez-Dominguez}%
\author[7]{Cesar Neira}%
\author[3]{Renato Aguiar}%
\author[8]{Ricardo Verdugo}%
\author[9]{Timothy O'Connor}%
\author[7]{Heinner Guio}%
\author[3]{Eduardo Tarazona-Santos}%
\author[3]{Thiago Leal}%
\author[10,11]{Fernanda Rodrigues-Soares}%
\affil[1]{Institute Oswaldo Cruz}%
\affil[2]{Universidade Federal do Triângulo Mineiro}%
\affil[3]{Universidade Federal de Minas Gerais}%
\affil[4]{Cayetano Heredia Pervuvian University}%
\affil[5]{Laboratório Nacional de Computação Científica}%
\affil[6]{INBIOMEDIC Research and Technological Center}%
\affil[7]{Instituto Nacional de Salud}%
\affil[8]{Universidad de Chile Facultad de Medicina}%
\affil[9]{University of Maryland School of Medicine}%
\affil[10]{UFTM - Universidade Federal do Triangulo Mineiro}%
\affil[11]{Federal University of Mineiro Triangle}%


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  \date{May 27, 2024}


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\begin{abstract}
The current search for host-susceptibility variants for COVID-19
contrasts with the fact that the study of the genetic architecture of
Severe Acute Respiratory Syndrome (SARS) has been neglected. For
human/SARS-CoV-2 interactome genes ACE2, TMPRSS2 and BSG, there is only
one 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.%
\end{abstract}%



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