Optical genome mapping identifies rare structural variations as predisposition factors associated with severe COVID-19.

Impressive global efforts have identified both rare and common gene variants associated with severe COVID-19 using sequencing technologies. However, these studies lack the sensitivity to accurately detect several classes of variants, especially large structural variants (SVs), which account for a substantial proportion of genetic diversity including clinically relevant variation. We performed optical genome mapping on 52 severely ill COVID-19 patients to identify rare/unique SVs as decisive predisposition factors associated with COVID-19. We identified 7 SVs involving genes implicated in two key host-viral interaction pathways: innate immunity and inflammatory response, and viral replication and spread in nine patients, of which SVs in STK26 and DPP4 genes are the most intriguing candidates. This study is the first to systematically assess the potential role of SVs in the pathogenesis of COVID-19 severity and highlights the need to evaluate SVs along with sequencing variants to comprehensively associate genomic information with interindividual variability in COVID-19 phenotypes.
Competing Interests: J.L., A.H., and A.C. are salaried employees of Bionano Genomics Inc. R.K. has received honoraria, travel funding, and research support from Illumina, Asuragen, QIAGEN, Perkin Elmer Inc, Bionano Genomics, and BMS. A.H.B. has received funding from the NIH, MDA (USA), AFM Telethon, Alexion Pharmaceuticals Inc., Audentes Therapeutics Inc., Dynacure SAS, and Pfizer Inc. He has consulted and received compensation or honoraria from Asklepios BioPharmaceutical Inc, Audentes Therapeutics, Biogen, F. Hoffman-La Roche AG, GLG Inc, Guidepoint Global, and Kate Therapeutics, and holds equity in Ballard Biologics and Kate Therapeutics.
(© 2022 The Author(s).)