颅内动脉瘤（Intracranial aneurysm, IA）为脑动脉血管的球囊性扩张膨胀，它影响2-5%的人群。IA破裂导致的蛛网膜下腔出血是目前最为严重的脑神经系统疾病之一。迄今为止，尚无有效的IA破裂预防手段，对IA的治疗也以有创的手术夹闭和栓塞为主，手术过程伴有很大风险。对IA病因、病理机制的研究是解决IA问题的关键。多项研究表明，IA具有明显的遗传易感性，遗传及环境因素共同作用最终导致IA的发生。我们前期完成了12个日本家系共计42例IA患者的外显子测序工作，从中筛选出了多个基因低频有害变异。这些聚集于家系病例中的低频有害变异，可能包含整体IA易感变异。本研究拟采用大样本病例-对照研究对这些基因低频变异进行筛选，以发现新的IA易感基因，并进行易感基因与环境因素的交互作用研究及生物学功能探讨，为IA的预防和治疗奠定基础。

The overall prevalence of intracranial aneurysm (IA) is estimated at 2-5% in the general population. The rupture of an IA is one of the most devastating neurological conditions known. There is no effective prevention and non-invasive treatment methods. The genetic predisposition of IA is largely unknown. Identification of the genetic factors involved is critical for disease prevention and treatment. With the aim to isolate the susceptibility genes for IA, we performed whole exome sequencing of 42 Japanese familial IA cases from 12 families. Preliminary study found that multiple less common damaging variants aggregated in familial IA. Further replicate association studies of these variants in additional IA cases are needed. We plan to do the association study using large cases and controls in order to identify IA susceptibility gene(s). Further gene-environment interaction analysis and functional study will be performed for susceptible genes (variants).