1 research outputs found
The ABO blood group locus and a chromosome 3 gene cluster associate with SARS-CoV-2 respiratory failure in an Italian-Spanish genome-wide association analysis
[Background] Respiratory failure is a key feature of severe Covid-19 and a critical driver of mortality, but for reasons poorly defined affects less than 10% of SARS-CoV-2 infected patients.[Methods] We included 1,980 patients with Covid-19 respiratory failure at seven centers in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe (Milan, Monza, Madrid, San Sebastian and Barcelona) for a genome-wide association analysis. After quality control and exclusion of population outliers, 835 patients and 1,255 population-derived controls from Italy, and 775 patients and 950 controls from Spain were included in the final analysis. In total we analyzed 8,582,968 single-nucleotide polymorphisms (SNPs) and conducted a metaanalysis of both case-control panels.[Results] We detected cross-replicating associations with rs11385942 at chromosome 3p21.31 and rs657152 at 9q34, which were genome-wide significant (P<5×10-8) in the meta-analysis of both study panels, odds ratio [OR], 1.77; 95% confidence interval [CI], 1.48 to 2.11; P=1.14×10-10 and OR 1.32 (95% CI, 1.20 to 1.47; P=4.95×10-8), respectively. Among six genes at 3p21.31, SLC6A20 encodes a known interaction partner with angiotensin converting enzyme 2 (ACE2). The association signal at 9q34 was located at the ABO blood group locus and a blood-group-specific analysis showed higher risk for A-positive individuals (OR=1.45, 95% CI, 1.20 to 1.75, P=1.48×10-4) and a protective effect for blood group O (OR=0.65, 95%
CI, 0.53 to 0.79, P=1.06×10-5).[Conclusions] We herein report the first robust genetic susceptibility loci for the development of respiratory failure in Covid-19. Identified variants may help guide targeted exploration of severe Covid19 pathophysiology.The IKMB's core facilities received infrastructure support by the
Deutsche Forschungsgemeinschaft (DFG) Cluster of Excellence "Precision Medicine in Chronic
Inflammation" (PMI, EXC2167). The project also received support through a philanthropic
donation by Stein Erik Hagen and Canica AS. L.V. was funded by the Fondazione IRCCS Ca’
Granda «COVID-19 Biobank» research grant. This
work was also supported by the Ministero dell’Istruzione, dell’Università e della Ricerca – MIUR
project "Dipartimenti di Eccellenza 2018 – 2022" (n° D15D18000410001) to the Department of
Medical Sciences, University of Torino. The IKMB authors
received financial support from the UKSH Foundation "Gutes Tun!" (special thanks to Alexander
Eck, Jenspeter Horst and Jens Scholz) and the German Federal Ministry of Education and Research
(BMBF; grant ID 01KI20197). HLA-Typing was performed and supported by the Stefan-MorschStiftung. M.A.H was supported by the Spanish Ministry of Science and Innovation ‘JdC fellowship
IJC2018-035131-I.N