Association of rare variants and intracranial aneurysm risk in a Chinese population.

Background: Genetic factors play important roles in the development of intracranial aneurysm (IA). Rare variants have been identified as being susceptible to Moyamoya disease (MMD), non-MMD intracranial artery stenosis/occlusion disease, and other vascular disorders. This study aimed to investigate the association between rare variants and the risk of IA in a Chinese population.

Methods: We recruited 174 patients with IA for target exome sequencing. Information on the control subjects was obtained from the 1,000 Genome Project and GeneSky in-house database. After prioritizing rare variants, the filtered variants were confirmed by Sanger sequencing. Gene-based association analyses were performed to identify the association between variants and the disease using burden and variance component methods; that is, the weighted-sum statistic (WSS) and the sequence kernel association test (SKAT), respectively. The Student's -test, Chi-squared test, and Fisher's exact test were used to compare the clinical characteristics between carriers and non-carriers of the variants.

Results: After filtering, there were 14 variants in 18 patients with IA, which were significantly associated with the disease after the gene-based association tests [minor allele frequency (MAF) <0.01, WSS P value 5.08×10; SKAT P value 2.96×10; SKAT-O P value 3.56×10]. Significant difference was not obtained between the carriers and non-carriers of the variants in terms of the clinical characteristics.

Conclusions: Rare variants were associated with sporadic IA in a Chinese population. Our findings suggest that these rare variants might have potentially important roles in IA. However, more comprehensive studies need to be conducted to confirm this association and causality.