| Population name | Horowitz_2 |
| Genome | GRCh38 |
| Consortium | Regeneron |
| Super population | EUR, AFR, SAS, EAS, |
| Population description | Cases were obtained from four studies (Geisinger Health System (GHS), Penn Medicine BioBank (PMBB), UK Biobank (UKB) and AncestryDNA) from five super population groups and grouped into five case-control comparisons related to the risk of infection and two others related to disease severity among cases with COVID-19. |
| Population origin | Study dependent |
| Case population size | 52630 |
| Control population size | 704016 |
| Comorbidities | not specified |
| Mean / median age | not specified |
| Sex | not specified |
| Severity | Combination |
| Sample source | NA |
| Method | Both common (minor allele frequency (MAF) > 0.5%, up to 13 million) and rare (MAF < 0.5%, up to 76 million) variants across the seven risk and severity phenotypes were considered |
| Bioinformatics | Ancestry-specific GWAS was performed in each study using the genome-wide Firth logistic regression test implemented in REGENIE V2.0.1. Firth’s approach is applied when the P value from the standard logistic regression score test is below 0.05. Directly genotyped variants with an MAF > 1%, <10% missingness, Hardy–Weinberg equilibrium test P > 1 × 10?15 and LD pruning (1,000 variant windows, 100 variant sliding windows and r2 < 0.9) were included. Covariates for age, age2, sex, age-by-sex and the first 10 ancestry-informative PC were also included. Results were subsequently meta-analyzed across studies and ancestries using an inverse variance-weighted fixed-effects meta-analysis. |
| Imputation details | AncestryDNA used the Haplotype Reference Consortium (HRC) reference panel and performed imputation with Minimac4 v.1.0.1. GHS and PMBB used the TOPMed reference panel using the TOPMed Imputation Server. |
| Limitations | 1. Greater power to identify associations with disease risk than with severity outcomes due to relatively small sample size for the latter, 2. Phenotypic heterogeneity among cases with COVID-19 and controls and associated risk factors due to four seperate studies with different collection variables. Ancestry DNA composed of more healthier individuals with milder COVID-19 compared to UKB, GHS and PMBB studies which collected in a clinical setting so were enriched for more severe cases. |