Table 2.
Burden associations among interferon signaling genes
| Variants included in burden test | Gene | Odds ratio (95% CI) | p value | N affected individuals with RR|RA|AA genotypea | N control individuals with RR|RA|AA genotypea | AAF | Heterogeneity p value |
|---|---|---|---|---|---|---|---|
| pLoF, MAF < 0.1% | IFNAR1 | 1.46 (0.51, 4.17) | 0.4786 | 4,775|5|0 | 549,164|374|0 | 0.00034 | 0.9111 |
| IFNAR2 | 1.96 (0.91, 4.19) | 0.0844 | 4,920|8|0 | 558,068|695|0 | 0.00062 | 0.0964 | |
| IKBKGb | 0.51 (0.04, 6.57) | 0.6048 | 4,394|0|0 | 500,582|32|10 | 0.00005 | 0.9584 | |
| IRF3 | 0.91 (0.39, 2.11) | 0.8293 | 4,924|3|1 | 558,279|483|1 | 0.00043 | 0.6339 | |
| IRF7 | 1.15 (0.57, 2.31) | 0.6975 | 4,920|8|0 | 557,892|871|0 | 0.00078 | 0.5267 | |
| IRF9 | 0.36 (0.02, 6.96) | 0.5024 | 4,478|0|0 | 530,571|58|0 | 0.00005 | 0.9996 | |
| STAT1 | 0.36 (0.01, 19.89) | 0.6207 | 4,394|0|0 | 500,584|40|0 | 0.00004 | 0.9996 | |
| STAT2 | 0.36 (0.07, 1.91) | 0.2311 | 4,644|0|0 | 541,214|144|0 | 0.00013 | 1.0000 | |
| TBK1 | 0.36 (0.04, 3.13) | 0.3553 | 4,478|0|0 | 530,539|90|0 | 0.00008 | 0.9995 | |
| TICAM1 | 0.81 (0.14, 4.73) | 0.8160 | 4,477|1|0 | 530,454|175|0 | 0.00016 | 0.7587 | |
| TLR3 | 1.56 (0.47, 5.13) | 0.4656 | 4,924|4|0 | 558,457|306|0 | 0.00027 | 0.7039 | |
| TRAF3 | 0.37 (0.0, 217.91) | 0.7576 | 4,394|0|0 | 500,597|27|0 | 0.00003 | 1.0000 | |
| UNC93B1 | 0.77 (0.28, 2.06) | 0.5974 | 4,641|3|0 | 540,929|429|0 | 0.00040 | 0.9294 | |
| all autosomal genes | 0.81 (0.56, 1.18) | 0.2709 | 4,655|23|0 | 514,810|3,219|0 | 0.00320 | 0.9492 | |
| pLoF and missense predicted deleterious, MAF < 0.1% | IFNAR1 | 1.51 (0.71, 3.18) | 0.2831 | 4,918|10|0 | 557,991|772|0 | 0.00069 | 0.8283 |
| IFNAR2 | 1.87 (0.88, 3.97) | 0.1021 | 4,920|8|0 | 558,045|718|0 | 0.00064 | 0.0862 | |
| IKBKGb | 1.48 (0.18, 12.34) | 0.7184 | 4,393|1|0 | 500,544|70|10 | 0.00009 | 0.6366 | |
| IRF3 | 0.9 (0.42, 1.92) | 0.7778 | 4,923|4|1 | 558,128|634|1 | 0.00057 | 0.7436 | |
| IRF7 | 1.15 (0.67, 1.96) | 0.6102 | 4,914|14|0 | 557,238|1,525|0 | 0.00137 | 0.3523 | |
| IRF9 | 0.36 (0.02, 6.96) | 0.5024 | 4,478|0|0 | 530,571|58|0 | 0.00005 | 0.9996 | |
| STAT1 | 0.35 (0.08, 1.49) | 0.1563 | 4,762|0|0 | 547,803|231|0 | 0.00021 | 1.0000 | |
| STAT2 | 1.26 (0.73, 2.2) | 0.4089 | 4,909|19|0 | 557,153|1,609|1 | 0.00145 | 0.7935 | |
| TBK1 | 1.0 (0.54, 1.85) | 0.9951 | 4,917|11|0 | 557,567|1,195|1 | 0.00107 | 0.6983 | |
| TICAM1 | 0.8 (0.14, 4.66) | 0.8084 | 4,477|1|0 | 530,451|178|0 | 0.00017 | 0.7558 | |
| TLR3 | 0.74 (0.49, 1.11) | 0.1396 | 4,911|17|0 | 556,016|2,745|2 | 0.00245 | 0.8319 | |
| TRAF3 | 1.7 (0.44, 6.62) | 0.4431 | 4,778|2|0 | 549,284|254|0 | 0.00023 | 0.1923 | |
| UNC93B1 | 0.92 (0.56, 1.5) | 0.7309 | 4,913|15|0 | 557,079|1,684|0 | 0.00151 | 0.9180 | |
| all autosomal genes | 0.94 (0.76, 1.17) | 0.5835 | 4,590|88|0 | 507,793|10,233|3 | 0.00990 | 0.5285 |
Association between the phenotype COVID-19 positive hospitalized versus COVID-19 negative or unknown and 13 genes (12 autosomal) related to interferon signaling that were recently reported to contain rare (MAF < 0.1%) deleterious variants in individuals with severe COVID-19.25 AAF, alternative allele frequency; CI, confidence interval.
RR, individuals who have genotype reference/reference for all variants included in burden test; RA, individuals who have genotype reference/alternate for at least one variant; AA, individuals who have genotype alternate/alternate for at least one variant.
IKBKG is located on the X chromosome. Hemizygous males are included in the N of individuals with two copies of the effect allele.