Association of Endothelin Receptor Type A with Intracranial Aneurysm in 20,609 East Asians: An Updated Meta-Analysis

Abstract

Genome-wide association studies have reported an association between the EDNRA gene and intracranial aneurysm (IA) in European and Japanese populations; however, there is no study on this polymorphism in other Asian populations. Therefore, we performed an extensive large-scale meta-analysis for association of the rs6841581 variant of EDNRA with IA susceptibility in East Asian population. We conducted a systemic review via electronic search for papers published between January 2002 and February 2019. We used fixed and random effect models and applied the inverse variance method. The statistical power of the result was estimated in the genome-wide significant threshold under an additive inheritance model. Our meta-analysis included 5873 patients with IA and 14,736 non-IA controls from 6 independent populations: 4 Japanese, 1 Chinese, and 1 Korean. The risk (major) G allele of rs6841581 showed the highest significant association with the increased risk of IA under the fixed effect model in the East-Asian population (odds ratio= 1.244, 95% confidence interval: 1.174-1.318, P= 1.36E-13). The rs6841581 variant showed sufficient statistical power (80.3%) in this meta-analysis under the additive model. In subsequent analysis, the frequencies of the risk G allele showed similar pattern in all of the Japanese, Chinese, and Korean populations (69%, 80%, and 78%, respectively). In the in silico functional analysis, none of the functional variants was correlated with rs6841581. The genetic variant of EDNRA, rs6841581, was significantly associated with increased risk of IA. Our findings indicate that it could be used as an IA-predicting variant in East Asian populations.