Abstract TP199: Genome Wide Association Study Of Intracranial Artery Dissection Reveals Potential Novel Loci

Abstract

Introduction: Cervico-cephalic dissections (extracranial artery dissection [EAD] and intracranial artery dissection [IAD]) are defined by a mural hematoma in the wall of a cervical or intracranial artery and represent an important cause of stroke in young adults. It is relatively uncommon in the general population and likely to represent the ethnic difference with higher frequency of IAD in Asian than European populations. A few studies examining the genetic contributions for these phenotypes were reported. In EAD, the PHACTR1 genes which had previously been identified as common genetic risk variants of hypertension and migraine was associated with EAD using genome-wide association study (GWAS) approaches. RNF213 , an important susceptibility gene for Moyamoya disease was associated with IAD in one small study (n=24) using a candidate-SNP analysis but no GWAS of IAD have been reported so far. We performed GWAS to identify common variants associated with IAD. Methods: A total of 100 Japanese patients with IAD based on imaging diagnostic criteria from multidisciplinary expert consensus were prospectively enrolled in National Cerebral and Cardiovascular Center from March 2011 to August 2018. Results: We performed GWAS in 100 IAD cases (61 men, 50 years of median age[IQR, 45-61]) and 8380 controls from the Tohoku Medical Megabank Project which is a publicly available healthy cohort. No variant reached to genome-wide significant but 14 variants (7 regions) showed nominal significant association with IAD (p < 10 -5 ). Among 14 variants, rs73828631 on RBMS3 gene showed highest association with IAD (odds ratio = 2.16, 95% confidence interval = 1.59-2.92; P = 3.08 х 10 -7 ). RBMS3 was previously identified as genetic loci associated with brain aneurysm. According to the Genotype-Tissue Expression (GTEx) project database, RBMS3 is highly expressed in artery. Conclusions: We identified potential 14 variants associated with IAD. We need to increase the number of IAD cases for further confirmation.