Genetic research at its best. From research idea to NEJM Paper in 3 months

To pull a genome-wide association study with more than 2000 cases and corresponding controls out of the ground in less than three months is quite admirable. But to do this at the time of a pandemic is even more admirable, especially when one considers that this study may provide clues to the genetic causes underlying this pandemic.  

It is known that there is considerable variability in disease behavior in SARS-CoV-2 infected patients. To identify potential genetic factors involved in Covid-19 development, David Ellinghaus and colleagues performed a GWAS of patients with severe disease identified by respiratory failure.

They included almost 2.000 patients with Covid-19 and respiratory failure at seven centers in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe for a GWAS.

In total they analyzed 8,5 Million SNPs and conducted a meta-analysis of both case-control panels.

The study detected cross-replicating associations with rs11385942 at chromosome 3p21.31 and rs657152 at 9q34.2, respectively.

At 3p21.31, the association signal spans the genes SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1. The association signal at 9q34.2 coincides with the ABO blood group locus, and in this cohort a blood-group-specific analysis showed higher risk for blood group A (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).

Andre and colleagues conclude, that they have identified a 3p21.31 gene cluster as a genetic susceptibility locus for Covid-19 with respiratory failure and confirm a potential involvement of the ABO blood group system.

Reassuringly, the Covid-19 Host Genetics Consortium data include the locus at chromosome 3p21.31 lends considerable support to their findings.  

This impressive study led by colleagues from Kiel (David Ellinghaus, Frauke Degenhardt, and Andre Franke) and Oslo (Tom H Karlsen), together with more than 100 colleagues from Italy and Spain is an amazing tour de force in genetics research, and I´m really honoured to be a very small part of it.   

My congratulations go to the team in Kiel, Oslo and, above all, to all the colleagues in Italy and Spain, in the epicenters of the pandemic, who made the study possible. A very big thank you goes to the patients, many of whom unfortunately will not have survived Covid19. Without the willingness of patients to participate, such genetic studies are not possible.

The manuscript is publicly available here: link

JE