A combination of variant genotypes at two loci in the APOL1 gene is associated with adverse outcomes in SARS-CoV-2: a UK Biobank study

Abstract

AbstractThe risk of hospitalisation or death from Covid-19 in the UK is disproportionately higher in black ethnic populations than others for reasons that are not fully understood1. In people of African ancestry, variants of the APOL1 gene (G1 and G2) have been associated with risk of a number of non-communicable diseases, such as chronic kidney disease2,3,4,5 and the infectious disease, African sleeping sickness6. Here we test the hypothesis that adverse Covid-19 outcomes are also associated with these variants.Using data from Black UK Biobank participants, we used Firth’s Bias-Reduced Logistic Regression in R to identify APOL1 genotypes that were associated with either hospitalisation or death. APOL1 G1/G2 compound heterozygotes were associated with hospitalisation (OR = 2.4 95% CI: 1.2-4.5) p = 0.010) and death (OR = 5.4, 95% CI: 1.8-15.4, p = 0.004) compared to individuals not carrying the variants. This support hypotheses proposing APOL1 genotype (specifically G1/G2) is a significant contributory factor in the increased rates of poor Covid-19 outcomes observed in people of African ancestry. This has implications for both at the individual and population level by identifying those at higher risk of severe Covid-19 who would benefit from early vaccination and treatment. This is especially relevant to geographical regions where APOL1 G1/G2 genotypes are common such as West and Central Africa6 and their diaspora.