Table 3.
Top results of the genome-wide burden analysis for rare variants increasing the risk of life-threatening COVID-19 under a recessive model
| Chr | Gene | Variant set | Type of variant | CADD > MSCa | GnomAD AF threshold | No. carriers of at least one rare homo-/hemizygous variant | Joint analysis | Trans-ethnic meta-analysis | Trans-pipeline meta-analysis | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Cases (n = 3269) | Controls (n = 1373) | OR[95%CI] | P value | ||||||||
| GW analysis | |||||||||||
| X | TLR7 | 7 | MISSLOF | FALSE | 0.01 | 51 | 2 | 8.41 [1.9–35.5] | 8.95 × 10−5 | 7.04 × 10−4 | 2.66 × 10−4 |
| 14 | AHNAK2 | 5 | MISSLOF | TRUE | 0.001 | 37 | 2 | 4.45 [1.1–17.7] | 0.01 | 2.15 × 10−3 | 8.84 × 10−3 |
| Refined analysis on TLR7 | |||||||||||
| X | TLR7 | bLOF | - | 0.01 | 20 | 0 | 27.68[1.5–528.7] | 1.1 × 10−4 | 6.6 × 10−3 | 2.7 × 10−4 | |
Only genes with P values ≤ 0.01 in the joint analysis and P values < 0.05 in trans-ethnic and trans-pipeline meta-analyses are displayed
AF allele frequency
aCombined Annotation Dependent Depletion (CADD) score [42] greater than the Mutation Significance Cut-off (MSC) for the corresponding gene. The MSC is defined for a given gene as the lower limit of the confidence interval (95%) of the CADD score of all its known pathogenic mutations [43]