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To date, the locus with the most robust human genetic association to COVID-19 severity is 3p21.31. Here, we integrate genome-scale CRISPR loss-of-function screens and eQTLs in diverse cell types and tissues to pinpoint genes underlying COVID-19 risk. Our findings identify  SLC6A20  and  CXCR6  as putative causal genes that modulate COVID-19 risk and highlight the usefulness of this integrative approach to bridge the divide between  correlational  and  causal  studies of human biology.   Supplementary Information  The online version contains supplementary material available at 10.1186/s13059-021-02454-4.

Integrative approach identifies SLC6A20 and CXCR6 as putative causal genes for the COVID-19 GWAS signal in the 3p21.31 locus