A GWAS in the pandemic epicenter highlights the severe COVID-19 risk locus introgressed by Neanderthals

Abstract

Large GWAS indicated that genetic factors influence the response to SARS-CoV-2. However, sex, age, concomitant diseases, differences in ancestry, and uneven exposure to the virus impacted the interpretation of data. We aimed to perform a GWAS of COVID-19 outcome in a homogeneous population whoexperienced a high exposure to the virus and with a known infection status. We recruited inhabitants of Bergamo province-that in spring 2020 was the epicenter of the SARS-Cov-2 pandemic in Europe-via an online questionnaire followed by personal interviews. Cases and controls were matched by age, sexand risk factors. We genotyped 1195 individuals and replicated the association at the3p21.31 locuswith severity, but with a stronger effect size that further increased in gravely ill patients. Transcriptome-wide association study highlighted eQTLs for LZTFL1 and CCR9. We also identified 17loci not previously reported, suggestive for an association with either COVID-19 severity or susceptibility.