FIGURE 1.

ACE2 expression among multiple GTEx tissues (A), comparison of the LD pattern of ACE2 GTEx expression quantitative trait loci (eQTLs) (minor allele frequency > 0.05) between EUR and CHB populations (B), and the association between rs2106809 with COVID-19 hospitalization in European population (C). In panel A, the ACE2 expression by sex among multiple GTEx tissues are demonstrated in violin plots. In adipose-subcutaneous and whole blood, the ACE2 expression is higher in females than in males; while in breast mammary tissue, the ACE2 expression is lower in females than in males (all p values < 0.01; ANOVA test). In panel B, there are 140 common eQTLs located in the genomic region of chrX: 15 284 068–16 013 888 (hg38). Only rs2106809 is a common SNP located in the promoter region of ACE2 (chrX: 15 597 069–15 607 069; hg38), which is highlighted by “*”. rs2106809 displays the similar LD pattern with other GTEx eQTLs in both EUR and CHB populations. The pairwise genotype correlation between all GTEx eQTLs was determined using Haploview, and their corresponding R ² values are shown with different colors, including red (R² > 0.8), yellow (R² between 0.5 and 0.8), blue (R² between 0.2 and 0.5), and green (R² < 0.2). In Panel C, rs2106809 along with two rare SNPs (rs62578876 and rs183546232) that are specific to EUR show an association with COVID-19 in the UK Biobank COVID-19 hospitalization GWAS of hospitalized cases (n = 1 712) vs. not hospitalized or tested negative samples (n = 56,988) in the EUR ancestry. rs2106809 minor allele G is protective against COVID-19 hospitalization (p = 0.047; beta = −0.07; se = 0.035), while the minor alleles of other two rare SNPs, including rs62578876 and rs183546232 (an intronic SNP of ACE2), are protective (p = 0.003; beta = −0.40; se = 0.13) and predisposing (p = 0.011; beta = 0.32; se = 0.12) to COVID-19 hospitalization, respectively. EUR: European; CHB: Chinese Han in Beijing.