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

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. Hosted file Manuscrito-2020-07-06.pdf available at https://authorea.com/users/340415/articles/467503human-sars-cov-2-interactome-and-human-genetic-diversity-tmprss2-rs2070788-associatedwith-severe-influenza-and-its-population-genetics-caveats-in-native-americans

Genetic association of TMPRSS2 rs2070788 polymorphism with COVID-19 case fatality rate among Indian populations

“…For the association study, we searched for the studies on TMPRSS2 gene variants reported in the literature elsewhere in relation to COVID-19 susceptibility ( Mollica et al, 2020 ; Andolfo et al, 2021 ; Asselta et al, 2020 ; Bhattacharyya et al, 2020 ; Darbani, 2020 ; Hou et al, 2020 ; Irham et al, 2020 ; Iyer et al, 2020 ; Jeon et al, 2020 ; Kim and Jeong, 2021 ; Latini et al, 2020 ; Paniri et al, 2021 ; Piva et al, 2021 ; Ragia and Manolopoulos, 2020 ; Senapati et al, 2020 ; Sharma et al, n.d. ; Singh et al, 2021 ; Strope et al, 2020 ; Torre-Fuentes et al, 2021 ; Vargas-Alarcón et al, 2020 ; Wang et al, 2020 ; Wulandari et al, 2021 ; Saih et al, 2021 ; Schönfelder et al, 2021 ; Kehdy et al, 2021 ) from this a total of 5 SNPs (rs2070788, rs734056, rs12329760, rs2276205, and rs3787950) was observed in our data and studied subsequently in detail. Data from the Estonian Biocentre ( Chaubey et al, 2017 ; Pathak et al, 2018 ; Re3data, 2014 ; Tätte et al, 2019 ), phase 3 of the 1000 Genomes Project ( Durbin et al, 2010 ), and our new genotyped samples from several Indian states were used to calculate the frequency of each of these SNPs among various Indian populations using plink 1.9.…”