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The genetic makeup of an individual contributes to susceptibility and response to infectious viruses. We describe the results of three genome-wide association meta-analyses comprising 49, COVID patients from 46 studies across 19 countries worldwide. They also represent potentially actionable mechanisms in response to infection. This working model of international collaboration a blue-print for future genetic discoveries in the event of pandemics or for any complex human disease.

Ganna: None. Highlight Session PL2. RNA sequencing RNA-seq , which directly probes gene expression defects, has emerged as a promising complementary tool increasing the diagnosis rate. By associating transcriptome aberrations with rare variants, we found a major role of nonsense-mediated decay in underexpression outliers and of coding and intronic variants in splicing outliers. Finally, we have gathered a reference dataset containing gene- and junction- level counts that can be integrated as controls for studies with small sample sizes.

Conclusion: Our study demonstrates the routine implementation of RNA-seq as a complementary tool to DNA sequencing for the diagnosis of rare diseases, paving the path towards more comprehensive OMICS-based diagnostics.