Disparities in COVID-19 severities and casualties across ethnic groups around the globe and patterns of ACE2 and PIR variants

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mediated Coronavirus disease-19 (COVID-19) has affected millions of individuals around all corners of the globe. Symptoms and severities of infection with this highly contagious virus vary among individuals and there is disparity in the number of COVID-19-related casualties across different ethnic groups. The primary receptor for SARS-CoV-2 entry into the host cells is angiotensin-converting enzyme 2 (ACE2). Certain variants of ACE2 are known to be associated with COVID-19 comorbidities such as hypertension, cardiovascular complications, diabetes, chronic lung disease, etc. In this study, we looked into the geographic distribution of disease-associated variants of ACE2 as well as closely located PIR gene to explore any possible correlation with the disparities in COVID-19 severities and casualties across ethnic groups. Frequencies of the ACE2 variants associated with COVID-19 comorbidities are higher in the European and the admixed American populations. These variants are also present with stronger pairwise linkage disequilibrium (LD) in the European and the admixed American populations. On the other hand, the variants with protective role are more prevalent in the East and the South Asian populations. Strong pairwise LD exists among the activity modifying (modifier) variants of the PIR and ACE2 genes only in the European super-population. Absence of these PIR variants in the South Asian population may contribute to the overall lower COVID-19 case fatality rates (CFR) despite the dense population in this region.

Keywords: ACE2; COVID-19; Genetic variants; Geographic distribution; Haplotype; Linkage disequilibrium; PIR; SARS-CoV-2.

Fig. 1

Pairwise LD among the disease associated variants of ACE2. LD measures are given as r². For the missing alleles in any population LD could not be calculated (NA). AFR = African, AMR = Admixed American, EAS = East Asian, EUR = European, SAS = South Asian.

Fig. 2

Pairwise LD among the modifier variants of ACE2 and PIR. LD measures are given as r². For the missing alleles in any population LD could not be calculated (NA). AFR = African, AMR = Admixed American, EAS = East Asian, EUR = European, SAS = South Asian.

Fig. 3

Multivariate clustering of populations based on disease-associated and modifier VAFs of ACE2 and PIR. Clustering was performed using unsupervised principal component analysis (PCA) method. Only the first three principal components (PCs) are shown in this fig. (5 PCs were considered). As shown in the Fig. 3, the first three components could explain most part of the variance (cumulative variance for the PC1, PC2 and PC3 is 98.1%).