Rho Guanine Nucleotide Exchange Factor ARHGEF17 Is a Risk Gene for Intracranial Aneurysms

Circulation. Genomic and Precision Medicine
Xinyu YangFuli Yu

Abstract

Intracranial aneurysm (IA) is usually a late-onset disease, affecting 1% to 3% of the general population and leading to life-threatening subarachnoid hemorrhage. Genetic susceptibility has been implicated in IAs, but the causative genes remain elusive. We performed next-generation sequencing in a discovery cohort of 20 Chinese IA patients. Bioinformatics filters were exploited to search for candidate deleterious variants with rare and low allele frequency. We further examined the candidate variants in a multiethnic sample collection of 86 whole exome sequenced unsolved familial IA cases from 3 previously published studies. We identified that the low-frequency variant c.4394C>A_p.Ala1465Asp (rs2298808) of ARHGEF17 was significantly associated with IA in our Chinese discovery cohort (P=7.3×10-4; odds ratio=7.34). It was subsequently replicated in Japanese familial IA patients (P=0.039; odds ratio=4.00; 95% confidence interval=0.832-14.8) and was associated with IA in the large Chinese sample collection comprising 832 sporadic IA-affected and 599 control individuals (P=0.041; odds ratio=1.51; 95% confidence interval=1.02-Inf). When combining the sequencing data of all familial IA patients from 4 different ethnicities (ie, Chinese,...Continue Reading

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Jul 13, 2018·Circulation. Genomic and Precision Medicine·Li HeWang Min
May 6, 2019·Neuromolecular Medicine·Zhen XuDong H Kim
May 19, 2019·Naunyn-Schmiedeberg's Archives of Pharmacology·Klaus AktoriesThomas Wieland
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Jul 13, 2021·Frontiers in Neurology·Junyu LiuJunxia Yan
Aug 18, 2021·Stroke; a Journal of Cerebral Circulation·Mark K Bakker, Ynte M Ruigrok

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