• Tatiana Foroud, Laura Sauerbeck, Robert Brown, Craig Anderson, Daniel Woo, Dawn Kleindorfer, Matthew L Flaherty, Ranjan Deka, Richard Hornung, Irene Meissner, Joan E Bailey-Wilson, Guy Rouleau, E Sander Connolly, Dongbing Lai, Daniel L Koller, John Huston, Joseph P Broderick, and FIA Study Investigators.
• Indiana University School of Medicine, Health Information and Translational Sciences Building - HS 4000, 410 West 10th Street, Indianapolis, IN 46202-3002, USA. tforoud@iupui.edu
• Stroke. 2008 May 1; 39 (5): 1434-40.

Background And PurposeEvidence supports a substantial genetic contribution to the risk of intracranial aneurysm (IA). The purpose of this study was to identify chromosomal regions likely to harbor genes that contribute to the risk of IA.MethodsMultiplex families having at least 2 individuals with "definite" or "probable" IA were ascertained through an international consortium. First-degree relatives of individuals with IA who were at increased risk of an IA because of a history of hypertension or present smoking were offered cerebral magnetic resonance angiography. A genome screen was completed using the Illumina 6K SNP system, and the resulting data from 192 families, containing 1155 genotyped individuals, were analyzed. Narrow and broad disease definitions were used when testing for linkage using multipoint model-independent methods. Ordered subset analysis was performed to test for a gene x smoking (pack-years) interaction.ResultsThe greatest evidence of linkage was found on chromosomes 4 (LOD=2.5; 156 cM), 7 (LOD=1.7; 183 cM), 8 (LOD=1.9; 70 cM), and 12 (LOD=1.6; 102 cM) using the broad disease definition. Using the average pack-years for the affected individuals in each family, the genes on chromosomes 4 (LOD=3.5; P=0.03), 7 (LOD=4.1; P=0.01) and 12 (LOD=3.6; P=0.02) all appear to be modulated by the degree of smoking in the affected members of the family. On chromosome 8, inclusion of smoking as a covariate did not significantly strengthen the linkage evidence, suggesting no interaction between the loci in this region and smoking.ConclusionsWe have detected possible evidence of linkage to 4 chromosomal regions. There is potential evidence for a gene x smoking interaction with 3 of the loci.

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