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

Area of Science:

• Genetics
• Epidemiology
• Infectious Diseases

Background:

• COVID-19 is associated with an increased risk of stroke, especially large artery stroke (LAS).
• The underlying biological mechanisms for this elevated risk remain unclear.
• This study investigates if SARS-CoV-2 infection mechanisms contribute to stroke risk.

Purpose of the Study:

• To explore the association between COVID-19 susceptibility and stroke subtypes.
• To determine if biological mechanisms related to SARS-CoV-2 infection are linked to increased stroke risk.

Main Methods:

• Constructed a polygenic risk score (PRS) for COVID-19 susceptibility.
• Tested PRS association with stroke subtypes using genetic data (SiGN, MEGASTROKE).
• Generated co-expression networks for SARS-CoV-2 uptake/infection genes and performed gene-based association testing.

Main Results:

• The COVID-19 susceptibility PRS was associated with LAS in both SiGN and MEGASTROKE datasets.
• The ISLR2 gene network, related to SARS-CoV-2 risk, showed significant association with LAS genetic risk in arteries and brain regions.

Conclusions:

• Genetic correlation and pathway enrichment suggest LAS risk in COVID-19 patients is linked to viral infection mechanisms.
• Findings indicate the increased LAS risk may be intrinsic to SARS-CoV-2 infection, not just severe illness.