Study population and setting
A total of 1,610 patients with severe COVID-19 defined by hospitalization with respiratory failure were recruited from seven medical centers in Spain and Italy, and compared to 2,205 randomly selected blood donors. Population based-controls were significantly younger than cases; data were unavailable regarding pre-existing comorbidities or other relevant risk factors for COVID-19.
Summary of Main Findings
A genome-wide association study (GWAS) estimated the association between ~8 million single nucleotide polymorphisms (SNPs) across the human genome, adjusting for population substructure, age, and sex separately by country and then combined with a fixed-effects meta-analysis. Two regions were identified and met the threshold of genome-wide significance (P<10^-8): a region on chromosome 3 upstream of a solute carrier (SLC6A209) and a region on chromosome 9 overlapping the ABO blood group gene. Further analyses found a protective effect for blood group O, and an elevated risk for A positive individuals.
By limiting cases to those hospitalized with documented COVID-19, the analysis is more likely to capture the host genetics underlying severe disease sequelae.
This study uses population controls that are not documented to be exposed or tested for COVID-19, which could dilute the true effect size. Additionally, the combination of different age distributions in cases and controls (controls being significantly younger), and the lack of availability of additional clinical information such as comorbidities, makes the association inference unclear. The associated genetic regions may reflect a COVID-19-specific morbidity, an existing co-morbidity, or generally poorer health in an older population.
This study provides evidence that genetic variants may be partially responsible for differences in COVID-19 severity.
This review was posted on: 25 June 2020