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Shared genetic background between SARS-CoV-2 infection and large artery stroke.

Int J Stroke. 2022 Apr 11:17474930221095696. doi: 10.1177/17474930221095696. Epub ahead of print. PMID: 35403514.

Authors/Editors: Parodi L, Myserlis EP, Chung J, Georgakis M, Mayerhofer E, Henry J, Montgomery B, Moy M, Xu H, Malik R, Langefeld C, Dichgans M, Woo D, Rosand J, Anderson CD.
Publication Date: 2022


Background and aims: Increased risk of stroke, particularly large artery stroke (LAS), has been observed in patients with COVID-19. The biological processes underlying the observed higher risk are still unknown. We explored the association between stroke subtypes and COVID-19 susceptibility to understand whether biological mechanisms specific to SARS-CoV-2 uptake/infection could be leading to excess stroke risk in this population.

Patients and methods: We constructed a polygenic risk score (PRS) of COVID-19 susceptibility and tested its association with stroke subtypes using individual- and summary-level genetic data (SiGN, MEGASTROKE). We generated co-expression networks of genes involved in SARS-CoV-2 uptake/infection (ACE2, TMPRSS2, BEST3, ISLR2 and ADAM17) based on existing tissue expression libraries. Gene-based association testing was performed using S PrediXcan and VEGAS2. Permutation independence tests were performed to assess SARS CoV-2-related gene enrichment in stroke and its subtypes.

Results: Our PRS demonstrated an association between COVID-19 susceptibility and LAS in SiGN (OR=1.05 per SD increase, 95% CI: [1.00, 1.10], p=0.04) and MEGASTROKE (β=0.510, 95% CI: [0.242, 0.779], FDR-p = 0.0019). The SARS-CoV-2 risk-related ISLR2 co-expression gene network was significantly associated with genetic risk of LAS in aorta, tibial arteries, and multiple brain regions (P < 0.05).

Conclusion: Presence of genetic correlation and significant pathway enrichment suggest that increases in LAS risk reported in COVID-19 patients may be intrinsic to the viral infection, rather than a more generalized response to severe illness.

Data access statement: The data and the code that support the findings of this study are available from the authors upon reasonable request.



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