Genomewide linkage in a large Dutch family with intracranial aneurysms: replication of 2 loci for intracranial aneurysms to chromosome 1p36.11-p36.13 and Xp22.2-p22.32

BACKGROUND AND PURPOSE: Approximately 2% of the general population harbor intracranial aneurysms. The prognosis after rupture of an intracranial aneurysm is poor; 50% of the patients die as a result of the rupture. Familial occurrence of intracranial aneurysms suggests there are genetic factors involved in the development of such aneurysms. METHODS: A large, consanguineous pedigree with 7 of 20 siblings affected by intracranial aneurysms was compiled and a genomewide linkage analysis on this family was performed using Illumina's single nucleotide polymorphism-based linkage panel IV, which includes 5861 single nucleotide polymorphisms. A nonparametric linkage affecteds-only approach with GENEHUNTER was used. RESULTS: Two loci with suggestive linkage (nonparametric linkage=3.18) on chromosome regions 1p36 and Xp22 were identified. Additional microsatellite markers were genotyped in the 2 candidate loci and showed suggestive linkage to the locus on chromosome 1 with a nonparametric linkage of 3.18 at 1p36.11-p36.13 and significant linkage to the locus on chromosome X with a nonparametric linkage of 4.54 at Xp22.2-p22.32. CONCLUSIONS: The 2 potential loci for intracranial aneurysms, which we identified in this large Dutch family, overlap with loci that have already been identified in previous linkage studies from different populations. Identification of genes from these loci will be important for a better understanding of the disease pathogenesis