A genome-wide association study for survival from a multi-centre European study identified variants associated with COVID-19 risk of death

Abstract

Genome-wide association; Survival; COVID-19

Asociación de todo el genoma; Supervivencia; COVID-19

Associació de tot el genoma; Supervivència; COVID-19

The clinical manifestations of SARS-CoV-2 infection vary widely among patients, from asymptomatic to life-threatening. Host genetics is one of the factors that contributes to this variability as previously reported by the COVID-19 Host Genetics Initiative (HGI), which identified sixteen loci associated with COVID-19 severity. Herein, we investigated the genetic determinants of COVID-19 mortality, by performing a case-only genome-wide survival analysis, 60 days after infection, of 3904 COVID-19 patients from the GEN-COVID and other European series (EGAS00001005304 study of the COVID-19 HGI). Using imputed genotype data, we carried out a survival analysis using the Cox model adjusted for age, age2, sex, series, time of infection, and the first ten principal components. We observed a genome-wide significant (P-value < 5.0 × 10−8) association of the rs117011822 variant, on chromosome 11, of rs7208524 on chromosome 17, approaching the genome-wide threshold (P-value = 5.19 × 10−8). A total of 113 variants were associated with survival at P-value < 1.0 × 10−5 and most of them regulated the expression of genes involved in immune response (e.g., CD300 and KLR genes), or in lung repair and function (e.g., FGF19 and CDH13). Overall, our results suggest that germline variants may modulate COVID-19 risk of death, possibly through the regulation of gene expression in immune response and lung function pathways.

Istituto Buddista Italiano Soka Gakkai funded A.R.’s and F.C.’s project “PAT-COVID: Host genetics and pathogenetic mechanisms of COVID-19” with the 8 × 1000 funds (ID n. 2020-226 2016_RIC_3), that, in part, included the present study. We also thank the generous contribution of Banca Intesa San Paolo to R.A. The funding organisations had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript.