An APOL1 genotype associated with adverse Covid- 19 outcomes: UK-Biobank data, September 2021

ABSTRACT

Introduction/ Background: The risk of hospitalisation/death from Covid-19 in the UK is disproportionately high in black populations. In people of African ancestry, variants of the APOL1 gene (G1 and G2) are associated with risk of noncommunicable diseases, and sleeping sickness. We hypothesise that adverse Covid-19 outcomes are also associated with these variants. Methods: The UK Biobank contains genetic, lifestyle, and health information from 7,643 individuals who self-report as being of black ethnicity. Within this cohort there had been 142 hospitalisations and 36 deaths attributed to Covid-19 as of September 2021. Taking risk factors previously associated with poor Covid-19 outcomes (age, sex, chronic kidney disease, atrial fibrillation, hypertension, depression, chronic obstructive pulmonary disease, dementia, type 2 diabetes, obesity, and Townsend deprivation index) as covariates, we used Firth's Bias Reduced Logistic Regression in R to identify APOL1 genotypes that were associated with hospitalisation and death. Results: Individuals who are heterozygous for variants at both the G1 and the G2 loci are termed G1/G2 compound heterozygotes. G1/G2 compound heterozygosity was associated with hospitalisation (odds ratio = 2.4, 95% confidence interval 1.2-4.5, p = 0.010) and death (odds ratio = 5.4, 95% confidence interval 1.8-15.4, p = 0.004). This association has not previously been detected in genome wide association studies, as they usually examine individual loci separately rather than considering combinations of loci. Impact This has implications 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 and G2 variants are common, such as West and Central Africa and their diaspora. Conclusion: This data supports hypotheses proposing APOL1 genotype (and specifically G1/G2 compound heterozygosity) as a significant contributory factor in the increased rates of poor Covid-19 outcomes observed in people of African ancestry.