A second update on mapping the human genetic architecture of COVID-19

In total, 15 out of 51 loci could be linked to three major pathways involved in susceptibility and severity defined by expert-driven classification (Supplementary Note): (1) viral entry; (2) entry defence in airway mucus; and (3) type I interferon response. [...]the phenome-wide association analysis identified nine loci involved in the upkeep of healthy lung tissue. [...]four loci contain candidate causal genes for entry defence in the airway mucus (Extended Data Fig. lb), such as previously reported MUC1/THBS3 (lq22) and MUC5B (lip 15.5) as well as novel MUC4 (3q29) and MUC16 (19pl3.2). [...]the previously reported locus lq22 contains an intergenic lead variant rsl2752585:G>A that decreases the risk of infection (OR = 0.98,95% CI = 0.97-0.98, P = 1.5 x 10_11) and increases MUCI expression in the oesophagus mucosa in GTEx v8 (P=5.2 x 10-9). [...]six loci contain candidate causal genes that are linked to the type I interferon pathway (Extended Data Fig. 1c), such as previously reported IFNAR2 (21q22.11), OAS1 (12q24.13) and TYK2 (19pl3.2), as well as additionally identified JAKI (lp31.3), IRF1 (5q31.1) and IFNa-coding genes (9p21.3).