COVID-19 host-genetics: Known and novel variants in an admixed population

Introduction: The investigation of host gene variants associated to COVID-19 has led to causal relationships and potential therapeutic targets, but most of these studies have taken place in individuals of European descent. Objective: Here, we aimed to confirm allele frequency differences in host genetic variants previously associated to COVID-19 in admixed individuals i.e., Mestizos from Mexico. Genes studied included those previously reported and replicated including, ABO, CCR2, CCR9, CXCR6, DPP9, FYCO1, IL10RB/IFNAR2, LZTFL1, OAS1, OAS2, OAS3, SLC6A20, TYK2, and XCR1. Methods: DNA from 106 COVID-19 patients and 2677 individuals were genotyped using the Illumina GSA array. Variants not probed in the array or that did not pass quality controls were imputed for these 14 genes using the 1000G phase 3 hg19 as reference following current standard protocols. Allele frequencies were computed and compared between COVID-19 patients and the general population. Results: We confirmed allele frequency differences for ABO rs657152, DPP9 rs2109069, LZTFL1 rs11385942, OAS1 rs10774671, OAS1 rs2660, OAS2 rs1293767, and OAS3 rs1859330 p<0.03. In addition, we identified over 100 SNVs with significant allele frequency differences (p-value <10 -2). Of these, there were four variants on ABO, OAS1/2 and FYCO1 with a high functional impact assessed in-silico. Conclusions: our observations confirm allele frequency differences in genes associated with COVID-19 in an admixed population and prompts for the development of metanalyses to validate local and geographical patterns of COVID-19 severity and infection associated to genetic variation.