Genomewide Linkage in a Large Caucasian Family Maps a New Locus for Intracranial Aneurysms to Chromosome 13q

Abstract

Background and Purpose— Familial aggregation of intracranial aneurysms (IAs) indicates a genetic role in the pathogenesis of this disease. Despite a number of reported susceptibility loci, no disease-causing gene variants have been identified. In this study, we used a parametric genomewide linkage approach to search for new IA susceptibility loci in a large Caucasian family. Methods— The affection status of family members with clinical signs of IA was confirmed with medical records or through radiological or surgical examinations. All other relatives were screened using MR angiography. Genomewide linkage analysis was performed on 35 subjects using approximately 250 000 single nucleotide polymorphic markers. Results— Ten individuals had an IA. Linkage analysis using a dominant model showed significant linkage to a 7-cM region in 13q14.12–21.1 with a maximum logarithm of odds score of 4.56. Conclusion— A new IA susceptibility locus on 13q was identified, adding to the number of IA loci already reported. Given that no coding variants have been reported to date, it is possible that alternative genetic variants such as regulatory elements or copy number variation are important in IA pathogenesis. We are proceeding with attempts to identify such variants in our locus.