A transcription regulatory network within the ACE2 locus may promote a pro-viral environment for SARS-CoV-2 by modulating expression of host factors

Tayaza Fadason; Sreemol Gokuladhas; Evgeniia Golovina; Daniel Ho; Sophie Farrow; Denis Nyaga; Hong Pan; Neerja Karnani; Conroy Wong; Antony Cooper; William Schierding; Justin M. O’Sullivan

The common variants that we tested show an unusual ancestry associated pattern of minor 173 allele frequencies ( Fig 1B) . Specifically, the East Asian population (1K Genomes project) 174 displays little variation across the bulk of the variants we analyzed. This observation is 175 supported by measures of genetic diversity (FST) between the Indian, Chinese and Malay 176 populations within the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort 177 (S3 Table) . However, this pattern breaks down at several positions across the ACE2 gene 178 (including rs4646142, rs2285666, and rs2106809, which show significant selection towards 179 the reference allele) in all of the tested populations, indicating potential selective pressure at 180 these loci (Fig 1B) . Notably, two of these variants alter potential transcription factor binding 181 sites (i.e. rs2285666 alters HNF1, and Ncx motifs, rs2106809 alters a CEBPB motif; S4 Table) . 182