| Population name | van Moorsel |
| Genome | GRCh38 |
| Consortium | Universities and hospital divisions in Netherlands, UK and Denmark |
| Super population | EUR |
| Population description | The discovery cohort from the ILD biobank and data registry of the St Antonius Hospital Nieuwegein, the Netherlands, included adult patients hospitalized due to COVID-19 at St Antonius Hospital between March 19, 2020 and May 5, 2020. 83 participants designated as White and 25 as non-White |
| Population origin | Netherlands |
| Case population size | 108 |
| Control population size | 611 |
| Comorbidities | 7% Diabetes, 15% Asthma/COPD, 1% Interstitial lung disease, 1% Pulmonary hypertension |
| Mean / median age | 66 |
| Sex | 69% male |
| Severity | Severe |
| Sample source | Nasopharyngeal and Clinical characteristics |
| Method | DNA was extracted using a Chemagic 360 from whole blood and samples were genotyped for MUC5B rs35705950 with a pre-designed taqman SNP genotyping assay and the QuantStudio R 5 Real-Time PCR system. Validation cohorts included 436 UKB cases and 356799 UKB controls. For replication, summary data from the severe COVID-19 GWAS group was obtained. This included 835 cases and 1255 controls from Italy and 775 cases and 950 controls from Spain. Genotype counts for SNP rs35705950 were obtained from the r |
| Bioinformatics | SPSS 24 was used for statistical analysis. Due to ethnic differences in the prevalence of the MUC5B rs35705950 alleles, genetic analyses were stratified by ethnicity and only statistically analyzed in white subjects. Differences between the allele and genotype frequencies were calculated with the Pearson’s goodness-of-fit chi-square test, together with the OR and 95% CI. Binary logistic regression was used to test for MUC5B rs35705950 association and COVID-19 with age and sex as confounding variables. A value of p < 0.05 was considered statistically significant. Metaanalyses were performed using the allele contrast and dominant model in the web tool META-Genyo. The fixed-effect estimate method, inverse variance was used. |
| Imputation details | Genetic data from the “v3” release of UKBB was used which contained the full set of Haplotype Reference Consortium (HRC) and 1000 Genomes imputed variants. For the Italian cohort imputation was performed via TOPMed reference panel |
| Limitations | a. A limitation of the study is the focus on white European populations. Minor allele frequencies for MUC5B rs35705950 are known to differ between populations, b. Small sample size of the Dutch cohort, yielding a significant result but with a wide confidence interval. |