Global patterns of genetic variation at genes involved in SARS-CoV-2 infection, and association with clinical phenotypes relevant to COVID-19

Event Details

  • Date:
  • Address: ,
  • Categories:

PRBB-CRG Sessions

by Arunag Verma and Chao Zhang, University of Pennsylvania


The COVID-19 pandemic caused by SARS-COV-2 infection has had a devastating impact on population health, with a disproportionate burden in minority populations. Transmission of the SARS-CoV-2 virus to humans requires its host receptor (i.e. ACE2) and other proteins in human host cells. We investigate nucleotide variation in genes that play a role in SARS-CoV-2 infection (ACE2, TMPRSS2, DDP4, and LY6E) in 2109 ethnically diverse Africans, 16,332 individuals from European and African ancestry from the Penn Medicine Biobank, and a comparative dataset of 2504 individuals from the 1000 Genomes project. We also explore the evolutionary forces underlying the global patterns of genetic variation. We identify 41 non-synonymous variants in ACE2 that are rare in most populations. However, we identify three common non-synonymous variants (rs138390800, rs147311723, and rs145437639) in the Central African hunter-gatherers (CAHG) from Cameroon with MAF ranging from 0.12 to 0.23 and we show signatures of positive selection on haplotypes containing these variants. Moreover, we observe a recent selection signature in the Khoesan populations from Botswana in the region upstream of ACE2 containing variants that are linked together and are most common (0.4 to 0.65) in the Khoesan. TMPRSS2 shows a positive selection signal with 11 non-synonymous variants fixed in humans compared with the Chimpanzee. We also identified several gene-disease associations with these SARS-CoV-2 infection candidate genes using electronic health record (EHR)-derived clinical phenotypes in the Penn Medicine Biobank . For example, ACE2 had association with respiratory failure and DPP4 was associated with upper respiratory tract infection. By characterizing genetic variation and clinical phenotype association at loci that may play a role in susceptibility to COVID-19 in ethnically diverse populations, we provide insights into identifying genetic risk factors for COVID-19 within and between populations


Hosted by Teresa D’Altri


Register here