Table 1. Significant (P<3.96×10-5) MR results.
| Gene | Tissue | beta | S.E. | P value | P het | Variants in instrument | Colocalization |
|---|---|---|---|---|---|---|---|
| IL10RB | Muscle Skeletal | 0.5078 | 0.0665 | 2.31E-14 | 0.9732 | rs2300370, rs2834167 | 0.98, <0.01 |
| IL10RB | Nerve Tibial | 0.2859 | 0.0384 | 9.76E-14 | 0.0052 | rs13050728, rs2834167, rs2266590 |
0.98, <0.01, <0.01 |
| CCR1 | Cells Cultured fibroblasts | 0.4449 | 0.0612 | 3.60E-13 | NA | rs13095940 | <0.01 |
| IL10RB | Brain Nucleus accumbens basal ganglia |
0.2541 | 0.0363 | 2.58E-12 | 0.0019 | rs2834167, rs17860115 | 0.75, 0.98 |
| IL10RB | Brain Caudate basal ganglia | 0.2635 | 0.0398 | 3.61E-11 | 0.0003 | rs2834167, rs1051393 | 0.01, 0.97 |
| IFNAR2 | Muscle Skeletal | 0.5881 | 0.0909 | 9.75E-11 | NA | rs2300370 | 0.98 |
| IL10RB | Brain Cerebellar Hemisphere | 0.1405 | 0.0229 | 8.22E-10 | 0.0389 | rs2834167, rs2236758 | 0.01, 0.95 |
| IL10RB | Breast Mammary Tissue | 0.6490 | 0.1079 | 1.82E-09 | NA | rs12053666 | 0.95 |
| IL10RB | Brain Frontal Cortex BA9 | 0.4667 | 0.0790 | 3.55E-09 | 0.0366 | rs2834167, rs1131668 | 0.14, 0.97 |
| IL10RB | Brain Cortex | 0.1929 | 0.0328 | 3.99E-09 | 0.0354 | rs2834167, rs1131668 | 0.02, 0.96 |
| CCR1 | Esophagus Gastroesophageal Junction |
0.1776 | 0.0302 | 4.11E-09 | NA | rs13059906 | 0.05 |
| IL10RB | Brain Cerebellum | 0.1147 | 0.0197 | 5.82E-09 | 0.0239 | rs2834167, rs1131668 | <0.01, 0.96 |
| CCR1 | Esophagus Mucosa | 0.4338 | 0.0751 | 7.60E-09 | NA | rs34059564 | <0.01 |
| IFNAR2 | Esophagus Mucosa | -0.4883 | 0.0865 | 1.63E-08 | NA | rs11911133 | 0.92 |
| PDE4A | Artery Aorta | -0.5420 | 0.0965 | 1.98E-08 | 0.0202 | rs370630099, rs45524632 | 0.41, 0.61 |
| IL10RB | Testis | 0.7104 | 0.1364 | 1.92E-07 | NA | rs2284550 | 0.11 |
| IFNAR2 | Skin not Sun Exposed Suprapubic | -0.3360 | 0.0671 | 5.46E-07 | NA | rs8127500 | <0.01 |
| IFNAR2 | Pancreas | -0.4708 | 0.0957 | 8.63E-07 | NA | rs1476415 | 0.06 |
| ACE2 | Brain Frontal Cortex BA9 | 0.1121 | 0.0233 | 1.56E-06 | NA | rs4830976 | 0.95 |
| IFNAR2 | Cells Cultured fibroblasts | -0.3893 | 0.0819 | 1.98E-06 | NA | rs1131668 | 0.92 |
| IL10RB | Cells Cultured fibroblasts | -0.5197 | 0.1093 | 1.98E-06 | NA | rs1131668 | 0.96 |
| CCR5 | Lung | -0.5868 | 0.1272 | 3.99E-06 | NA | rs12639314 | 0.02 |
| IL10RB | Esophagus Gastroesophageal Junction |
0.4678 | 0.1052 | 8.80E-06 | NA | rs56079299 | 0.96 |
Significant Mendelian randomization results, P<3.96×10-5 (0.05 Bonferroni-corrected for 1,263 actionable druggable genes). Mendelian randomization estimates were calculated using inverse-variance weighting and fixed effects for instruments that contained more than one variant, and Wald-ratio for instruments with one variant. All results used cis-eQTL instruments and no results using cis-pQTL instruments yielded results P<3.96×10-5. Phet refers to the heterogeneity P value across individual-variant MR estimates within a genetic instrument calculated using the Cochrane Q method, therefore instruments containing one variant were not tested for not tested for heterogeneity. A positive beta estimate indicates that more gene expression is associated with higher risk of COVID-19 hospitalization. “Colocalization” indicates PP.H4 between eQTLs and COVID-19 hospitalization. For example, for IL10RB in skeletal muscle, the primary GWAS with rs2300370 as the peak cis-eQTL colocalizes with COVID-19 hospitalization at PP.H4=0.98, and the secondary GWAS (i.e. after adjusting for rs2300370) with rs2834167 as the peak cis-eQTL does not colocalize with COVID-19 hospitalization (PP.H4<0.01).