Journal article
Genome screen to detect linkage to intracranial aneurysm susceptibility genes: the Familial Intracranial Aneurysm (FIA) study
Stroke (1970), Vol.39(5), pp.1434-1440
05/2008
DOI: 10.1161/STROKEAHA.107.502930
PMCID: PMC2435164
PMID: 18323491
Abstract
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.
Details
- Title: Subtitle
- Genome screen to detect linkage to intracranial aneurysm susceptibility genes: the Familial Intracranial Aneurysm (FIA) study
- Creators
- Tatiana Foroud - Indiana University School of Medicine, Health Information and Translational Sciences Building - HS 4000, 410 West 10th Street, Indianapolis, IN 46202-3002, USA. tforoud@iupui.eduLaura SauerbeckRobert BrownCraig AndersonDaniel WooDawn KleindorferMatthew L FlahertyRanjan DekaRichard HornungIrene MeissnerJoan E Bailey-WilsonGuy RouleauE Sander ConnollyDongbing LaiDaniel L KollerJohn Huston IIIJoseph P BroderickFamilial Intracranial Aneurysm (FIA) Study Investigators
- Contributors
- Colin P Derdeyn (Contributor) - University of Iowa, Radiology
- Resource Type
- Journal article
- Publication Details
- Stroke (1970), Vol.39(5), pp.1434-1440
- Publisher
- United States
- DOI
- 10.1161/STROKEAHA.107.502930
- PMID
- 18323491
- PMCID
- PMC2435164
- ISSN
- 0039-2499
- eISSN
- 1524-4628
- Grant note
- N01HG65403 / NHGRI NIH HHS R01 NS039512 / NINDS NIH HHS T32 NS047996 / NINDS NIH HHS R01 NS39512 / NINDS NIH HHS R01 NS039512-05 / NINDS NIH HHS
- Language
- English
- Date published
- 05/2008
- Academic Unit
- Neurology; Radiology; Iowa Neuroscience Institute; Neurosurgery
- Record Identifier
- 9984014023002771
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