Genome Screen to Detect Linkage to Intracranial Aneurysm Susceptibility Genes
- 1 May 2008
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Stroke
- Vol. 39 (5), 1434-1440
- https://doi.org/10.1161/strokeaha.107.502930
Abstract
Background and Purpose— Evidence 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. Methods— Multiplex 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×smoking (pack-years) interaction. Results— The 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. Conclusions— We have detected possible evidence of linkage to 4 chromosomal regions. There is potential evidence for a gene×smoking interaction with 3 of the loci.Keywords
This publication has 36 references indexed in Scilit:
- Association Analysis of Common Variants of ELN, NOS2A, APOE and ACE2 to Intracranial AneurysmStroke, 2006
- Examination of ELN as a Candidate Gene in the Utah Intracranial Aneurysm PedigreesStroke, 2005
- Ignoring Linkage Disequilibrium among Tightly Linked Markers Induces False-Positive Evidence of Linkage for Affected Sib Pair AnalysisAmerican Journal of Human Genetics, 2004
- Ordered subset analysis in genetic linkage mapping of complex traitsGenetic Epidemiology, 2004
- Confirmation of chromosome 7q11 locus for predisposition to intracranial aneurysmHuman Genetics, 2004
- Elastin Polymorphism Haplotype and Intracranial Aneurysms Are Not Associated in Central EuropeStroke, 2003
- Parametric and nonparametric linkage analysis: a unified multipoint approach.1996
- Familial subarachnoid hemorrhage: Distinctive features and patterns of inheritanceAnnals of Neurology, 1995
- Familial aneurysmal subarachnoid hemorrhage: a community-based studyJournal of Neurosurgery, 1995
- Subarachnoid Hemorrhage and Family HistoryArchives of Neurology, 1995