Genetic dissection of familial intracranial aneurysms by family-based approach

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In the study from 2002 to 2004, we have investigated 5 projects. First, we had recruited a study cohort of patients with familial histories of intracranial aneurysms (IA). Second, we conducted linkage analysis in these pedigrees. Third, we recruited cases and controls for the association study. Fourth, we conducted a replicating study for genes reported to be associated with IAs. Finally, we have tested whether a candidate gene found in pedigree study is associated with IA by a case-control study.1. A study cohort of pedigrees with familial IA : 29 families were recruited. From these families, 169 members took MRA screening. In these families, 104 members were found to have IA. Totally 273 members joined this study.2. Linkage analysis : We have conducted a linkage analysis for 29 families. The result revealed three significant regions : 17cent,19q13,and Xp22.3. A population for case-control study. Cases were defined as those who have been found to have IA by MRA/MRI or 3DCT angiography or angiography or been found to have IA by surgery for SAH. Controls were defined as those who were not having IA by MRA/MRI, are older than 40 years and are without family histories or histories of cerebrovascular diseases. Finally, we recruited 362 members and 332 members for cases and controls, respectively.4. A replication study : We have tested whether genes previously reported could be replicated or not. We selected Elastin (7q11), NOS2A(17cent), APOE (19q13) and ACE2(Xp22). We failed to replicate none of these genes in our population.5. Genes on 17cent : There are 108 genes on the linked region of chromosome 17cent. We selected 9 genes (TNFRSF13,M-RIP, COPS3,RAI1,SREBF1,GRAP MAPK7,MFPK7 and AKAP10) from this region. We conducted family study and case control studies'. A significant linkage and association was confirmed for TNFRSF13B.