Identification of an autosomal dominant locus for intracranial aneurysm through a model-based family collection in a geographically limited area

Intracranial aneurysm (IA) is characterized by an abnormal bulging of one of the arteries in the brain and is heavily affected by genetic factors. Although IA is a very serious disease because of its severity and prevalence in the general public, the gene causing IA has not yet been identified due mainly to the lack of definitive genetic loci for the disease. Following a model-based family collection that recruited families from a geographically limited area that inherited IA as an autosomal dominant trait, we conducted a genome-wide linkage analysis. Significant evidence of linkage to IA was found on chromosome 8p22.2 with a maximum two-point logarithm of the odds ratio score of 3.61 under an autosomal dominant model of inheritance. The methods described in this study could be applied to localize disease-causing genes of other complex diseases through either a genome-wide linkage analysis or a genome-wide association study.