Table 2.
Association between the phenotype COVID-19 positive and hospitalized (cases) vs COVID-19 negative or unknown (controls) and 14 genes related to interferon signaling that were recently reported to contain rare (MAF<0.1%), deleterious variants in patients with severe COVID-19 [14, 23].
| Variants included in burden test | Gene | Odds Ratio (95% CI) | P-value | N cases with RR|RA|AA genotype* | N controls with RR|RA|AA genotype* | AAF |
|---|---|---|---|---|---|---|
| pLoF, MAF<0.1% | IFNAR1 | 0.805[0.146;4.438] | 8.00E-01 | 2019|1|0 | 525406|359|0 | 0.00034 |
| IFNAR2 | 2.077[0.620;6.961] | 2.40E-01 | 2082|3|0 | 534277|688|0 | 0.00064 | |
| IKBKG | 0.491[0.005;50.219] | 7.60E-01 | 1873|0|0 | 508491|31|10 | 0.00005 | |
| IRF3 | 0.956[0.251;3.643] | 9.50E-01 | 2083|2|0 | 534559|406|0 | 0.00038 | |
| IRF7 | 1.165[0.426;3.185] | 7.70E-01 | 2082|3|0 | 534124|841|0 | 0.00079 | |
| IRF9 | 0.371[0.003;53.766] | 7.00E-01 | 1873|0|0 | 508479|53|0 | 0.00005 | |
| STAT1 | 0.365[0.001;126.712] | 7.40E-01 | 1873|0|0 | 508490|42|0 | 0.00004 | |
| STAT2 | 0.355[0.028;4.438] | 4.20E-01 | 1873|0|0 | 508405|127|0 | 0.00012 | |
| TBK1 | 0.365[0.011;11.964] | 5.70E-01 | 1873|0|0 | 508445|87|0 | 0.00009 | |
| TICAM1 | 3.730[0.189;73.610] | 3.90E-01 | 1872|1|0 | 508368|164|0 | 0.00016 | |
| TLR3 | 1.128[0.144;8.834] | 9.10E-01 | 2084|1|0 | 534674|291|0 | 0.00027 | |
| TLR7 | 7.627[1.872;31.075] | 4.60E-03 | 1872|0|1 | 508503|25|4 | 0.00003 | |
| TRAF3 | 0.368[0.000;733.638] | 8.00E-01 | 1873|0|0 | 508504|28|0 | 0.00003 | |
| UNC93B1 | 1.302[0.272;6.238] | 7.40E-01 | 1938|2|0 | 516861|409|0 | 0.0004 | |
| pLoF or missense predicted deleterious, MAF<0.1% | IFNAR1 | 0.756[0.234;2.444] | 6.40E-01 | 2083|2|0 | 534219|746|0 | 0.0007 |
| IFNAR2 | 1.968[0.598;6.469] | 2.70E-01 | 2082|3|0 | 534253|712|0 | 0.00067 | |
| IKBKG | 0.446[0.010;19.737] | 6.80E-01 | 1873|0|0 | 508452|70|10 | 0.00009 | |
| IRF3 | 0.786[0.238;2.592] | 6.90E-01 | 2083|2|0 | 534413|552|0 | 0.00052 | |
| IRF7 | 1.137[0.519;2.492] | 7.50E-01 | 2080|5|0 | 533486|1479|0 | 0.00138 | |
| IRF9 | 0.371[0.003;53.766] | 7.00E-01 | 1873|0|0 | 508479|53|0 | 0.00005 | |
| STAT1 | 0.365[0.038;3.488] | 3.80E-01 | 2018|0|0 | 526009|218|0 | 0.00021 | |
| STAT2 | 2.600[1.272;5.314] | 8.80E-03 | 2073|12|0 | 533405|1559|1 | 0.00146 | |
| TBK1 | 1.114[0.445;2.790] | 8.20E-01 | 2081|4|0 | 533861|1103|1 | 0.00103 | |
| TICAM1 | 3.657[0.188;71.218] | 3.90E-01 | 1872|1|0 | 508365|167|0 | 0.00016 | |
| TLR3 | 0.805[0.435;1.493] | 4.90E-01 | 2077|8|0 | 532355|2609|1 | 0.00244 | |
| TLR7 | 1.580[0.627;3.979] | 3.30E-01 | 2001|3|1 | 525830|477|163 | 0.00076 | |
| TRAF3 | 3.013[0.527;17.217] | 2.10E-01 | 2019|1|0 | 525523|242|0 | 0.00023 | |
| UNC93B1 | 1.665[0.774;3.582] | 1.90E-01 | 2075|10|0 | 533331|1634|0 | 0.00153 |
*
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.