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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
  • +21
  • Fernanda Kehdy,
  • Murilo Pita-Oliveira,
  • Mariana Scudeler,
  • Sabrina Torres-Loureiro,
  • Camila Zolini,
  • Rennan Moreira,
  • Lucas Michelin,
  • Isabela Alvim,
  • Carolina Silva-Carvalho,
  • Vinicius Furlan,
  • Marla Aquino,
  • Meddly Santollala,
  • Victor Borda,
  • Giordano Soares-Souza,
  • Luis Jaramillo-Valverde,
  • Andres Vasquez-Dominguez,
  • Cesar Neira,
  • Renato Aguiar,
  • Ricardo Verdugo,
  • Timothy O'Connor,
  • Heinner Guio,
  • Eduardo Tarazona-Santos,
  • Thiago Leal,
  • Fernanda Rodrigues-Soares
Fernanda Kehdy
Institute Oswaldo Cruz
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Murilo Pita-Oliveira
Universidade Federal do Triângulo Mineiro
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Mariana Scudeler
Universidade Federal do Triângulo Mineiro
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Sabrina Torres-Loureiro
Universidade Federal do Triângulo Mineiro
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Camila Zolini
Universidade Federal de Minas Gerais
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Rennan Moreira
Universidade Federal de Minas Gerais
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Lucas Michelin
Universidade Federal de Minas Gerais
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Isabela Alvim
Universidade Federal de Minas Gerais
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Carolina Silva-Carvalho
Universidade Federal de Minas Gerais
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Vinicius Furlan
Universidade Federal de Minas Gerais
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Marla Aquino
Universidade Federal de Minas Gerais
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Meddly Santollala
Cayetano Heredia Pervuvian University
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Victor Borda
Laboratório Nacional de Computação Científica
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Giordano Soares-Souza
Universidade Federal de Minas Gerais
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Luis Jaramillo-Valverde
INBIOMEDIC Research and Technological Center
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Andres Vasquez-Dominguez
INBIOMEDIC Research and Technological Center
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Cesar Neira
Instituto Nacional de Salud
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Renato Aguiar
Universidade Federal de Minas Gerais
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Ricardo Verdugo
Universidad de Chile Facultad de Medicina
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Timothy O'Connor
University of Maryland School of Medicine
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Heinner Guio
Instituto Nacional de Salud
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Eduardo Tarazona-Santos
Universidade Federal de Minas Gerais
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Thiago Leal
Universidade Federal de Minas Gerais
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Fernanda Rodrigues-Soares
Federal University of Mineiro Triangle, UFTM - Universidade Federal do Triangulo Mineiro
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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.