颅内动脉瘤(intracranial aneurysm，IA)破裂出血可导致很高的病残率和病死率，其生成机制与遗传学密切相关。IA相关易感基因是目前IA遗传学研究热点，已发现若干与IA相关的易感基因。最新的高通量全基因组测序技术能全面挖掘 DNA 水平的遗传变异，为IA研究提供最全面的遗传信息。本组前期在家族性IA病人群中发现位于17号染色体上MAP2K3 和KCNJ18基因存在错义突变、位于11号染色体上CREB3L1基因存在移码缺失等，为探寻新的IA易感基因打下了基础。本课题将在此基础上扩大家族性IA样本进行全基因组测序和生物信息学分析；在散发IA中利用SNP分型等技术，进一步确定新的脑动脉瘤相关易感基因；检测脑动脉瘤壁组织相关易感基因的表达，验证其与IA发生的相关性。从而筛选出新的IA易感基因，为研究IA发病及遗传机制提供重要信息，为临床IA预防、诊断和治疗提供新依据和新靶点。

Ruptured intracranial aneurysm (IA) can cause high morbidity and mortality, its formation mechanism is closely related with genetics. IA related predisposing genes are the research focus in IA genetics study, which have found that some susceptibility genes are associated with IA occurrence. Whole genome sequencing, the new high-throughput sequencing technology, can deeply excavate genetic variation at DNA level, to provide the most comprehensive genetic information for IA research. Our group has found that there are missense mutations on MAP2K3 and KCNJ18 gene located in chromosome 17, frameshift mutations on CREB3L1 gene located in chromosome 11 in familial IA patients, laying the groundwork for exploring new IA predisposing genes. On this basis, the extended FIA samples for whole genome sequencing and bioinformatics analysis; Verification genetic variation with the technology of SNP Typing in extended sporadic IA samples, further to determine the new brain aneurysm related susceptibility gene expression; detection of related susceptibility gene in intracranial aneurysm wall tissue to verify its correlation with the occurrence of IA. Our woke could screen out the new IA related predisposing genes, providing important information for the study of IA pathogenesis and genetic mechanism, providing new evidence and new targets for clinical prevention, diagnosis and treatment of IA.