ABSTRACT
Background and aims: SARS-CoV2 infection may increase stroke risk. The biological mechanisms underlying ischemic stroke occurrence during COVID-19 remains unclear. Methods: A Genome-Wide Association Study (GWAS) from MEGASTROKE was used to generate Polygenic risk scores (PRSs) across four p-value thresholds (p=0.05-p=5e-8) using PRSice-2. For all ischemic stroke (AIS) we used 34217 cases and 406111 controls, large-artery atherosclerosis (LAA) 4373 cases 297290 controls, cardioembolic (CE) 7193 cases 355468 controls and small-vessel occlusion (SVO) 5386 cases 343560 controls. For undetermined stroke etiology (UND) 984 cases and 5590 controls from a Spanish stroke cohort were used. PRSs were tested in 54 patients with an ischemic stroke that occurred after COVID-19 hospitalization (<8 days)(IS-COV). IS-COV cases were genotyped with Axiom Spain Biobank Array (11 UND, 6 CE, 6 LAA, 5 SVO, 2 infrequent cause and 24 unknown etiology). 726 population controls were also genotyped. Results: We found significant associations of IS-COV with PRSAIS (threshold= 5e-5, p= 0.04;R2= 0.01, number of SNPs= 60), PRSCE (threshold= 5e-8, p= 0.02, R2= 0.01, SNPs= 4;threshold= 0.05, p= 5.9e-4, R2= 0.03, SNPs=19308), PRSLAA (threshold= 5e-5, p= 6.5e-3, R2= 0.02, SNPs= 81;threshold= 1e-4, p= 0.02, R2= 0.01, SNPs= 146;threshold= 0.05, p =1.3e-3, R2= 0.03, SNPs= 20722) and PRSUND (threshold= 1e-4, p= 0.04, R2= 0.01, SNPs=10;threshold= 0.05, p =1.5e-6, R2= 0.06, SNPs= 3416). We did not find any association between PRSSVO and IS-COV. Conclusions: CE, LAA and UND shared genetic mechanisms with ischemic stroke cases due to COVID-19. We found no association between SVO and IS-COV.