Thread by @covid19_hgi

Our @covid19_hgi flagship paper is OUT NOW on medrxiv!

medrxiv.org/content/10.110…

In numbers:
50,000 SARS-COV-2 patients
46 participating studies
19 countries represented
15 loci identified
2,870 authors

#Covid19 #Genetics #Sarscov2 #immunology #scicomm #DNA

Our study objective was to form a global network of investigators to identify genetic factors influencing SARS-COV-2 infection and severe manifestations of COVID-19.

We defined 3 COVID-19 phenotypes:
(1) critically ill needing respiratory support
(2) hospitalized
(3) all reported infections incl. asymptomatic and mild cases

Analyses Included:
Genome-wide meta-analyses
Phenome-wide association study
Heritability
Genetic Correlation
Mendelian Randomization

Fig 1:
Incredible collaboration of 46 studies from 19 countries, with up to 49,562 COVID-19 cases and 2 million controls

3 COVID-19 phenotypes:
1. critically ill needing respiratory support
2. hospitalized
3. all reported infections incl. asymptomatic and mild cases

@ma_niemi

Fig 2: 15 genomic regions associated with COVID-19 phenotypes. Of these, 11 regions affect progression to severe disease (top panel in yellow) incl. chr3 region & 4 regions affect general susceptibility to infection (bottom panel in green) incl. ABO locus @JuhaMehtonen @ma_niemi

Fig 2 cont'd: We also conducted a meta-analysis comparing hospitalized cases with mildly symptomatic/asymptomatic individuals. For the 11 loci associated with severity, effect sizes did not significantly differ when using better refined controls vs. population controls @masakanai

Fig 3a: We combined 5 metrics to prioritize candidate causal genes of each locus, e.g. correlation with deleterious/eQTL variants.

Candidates include (but aren't limited to):
TYK2 and PPP1R15A (coding variants)
FOXP4, ABO, OAS1/2/3 and IFNAR2/IL10RB (lung eQTL).
@GitaPathakPhD

Fig3b: Phenotypes for GWAS lead variants in LD (r2>0.8) with COVID-19 index variants highlighted lung-related function and outcomes, also implicating metabolic, inflammatory, and blood traits. @SheaJAndrews

Fig. 4: We used genetic correlation and Mendelian randomization to investigate the causal associations between 38 traits and COVID-19. We found four traits with robust causal estimates, including BMI, smoking, height, and red blood cell count. @RenatoPolimanti @GitaPathakPhD

In summary, we identified 15 loci associated with SARS-CoV-2 infection or COVID-19 severity. Several of these loci were previously implicated in lung or autoimmune & inflammatory disease. Further, smoking & BMI were identified as causal risk factors for severe COVID-19

Mark your calendars:

Next Data Freeze is April 15