Results from a genome-wide study published in the New England Journal of Medicine identifies gene cluster 3p21.31 as a genetic susceptibility locus in patients with respiratory failure and the potential involvement of the ABO blood-group system.
A genome-wide association study was conducted involving 835 Italian patients with severe COVID-19 (defined as respiratory failure), 1,255 control blood donor participants, and 775 patients and 950 control participants from Spain. A total of 8,582,986 single-nucleotide polymorphisms (SNPs) were analysed. A meta-analysis of two control panels, derived from previous studies, from people with unknown SARS-CoV-2 infection, was also conducted.
Cross-replicating associations were detected with rs11385942 at locus 3p21.31 and with rs657152 at locus 9q34.2, which were significant at the genome-wide level (P−8) in the meta-analysis of the two case-control panels. The association signal at locus 9q34.2 coincided with the ABO blood group locus. A blood-group-specific analysis showed a higher risk in blood group A than in other blood groups, and a protective effect in blood group O as compared with other blood groups.
Further exploration of these findings is warranted both for clinical risk profiling of patients with COVID-19 and to understand the underlying pathophysiology.