A Genome Wide Association Study In Patients With Intracranial Atherosclerosis

Background and Aims: Large-artery intracranial atherosclerosis (ICAs) is a major cause of stroke worldwide. Genome-Wide Association studies (GWAs) have identified 6 loci associated with large-artery stroke. However, no GWAs has been performed to identify genetic variants associated with ICAs. Our aim is to find genetic risk factors associated with ICAs using a GWAs approach. Methods: We analyzed 107 patients with ICAs (94.6%symptomatic) and 316 population-based controls and replicated the results in two cohorts of 444 and 1,270 stroke patients attributed to intracranial and extracranial atherosclerosis, respectively, and 25,643 controls from the SiGN study. Genetic analysis was performed using HumanCoreExome(Illumina). For quality controls (QC), imputation and association analysis we used PLINK, R, IMPUTE2 and SNPTEST following previous recommendations. We included sex, age and principal components as covariates. For significant polymorphisms, we used GTEx to find eQTLs and SOMASCAN to find associations with protein levels(1,305 proteins in 52 plasma subjects).Results: After QC, we analyzed 8,047,349 single-nucleotide polymorphisms (SNPs). One locus at 18q22 (with three independent SNPs) was associated (P