Genome screen to detect linkage to intracranial aneurysm susceptibility genes: The familial intracranial aneurysm (FIA) study

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

Research output: Contribution to journalArticle

39 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1434-1440
Number of pages7
JournalStroke
Volume39
Issue number5
DOIs
StatePublished - May 1 2008

Fingerprint

Intracranial Aneurysm
Genome
Smoking
Chromosomes, Human, Pair 4
Genes
Chromosomes, Human, Pair 8
Cerebral Angiography
Magnetic Resonance Angiography
Information Systems
Single Nucleotide Polymorphism
Hypertension

Keywords

  • Intracranial aneurysm
  • Linkage
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing
  • Medicine(all)

Cite this

Genome screen to detect linkage to intracranial aneurysm susceptibility genes : The familial intracranial aneurysm (FIA) study. / Foroud, Tatiana; Sauerbeck, Laura; Brown, Robert; Anderson, Craig; Woo, Daniel; Kleindorfer, Dawn; Flaherty, Matthew L.; Deka, Ranjan; Hornung, Richard; Meissner, Irene; Bailey-Wilson, Joan E.; Rouleau, Guy; Connolly, E. Sander; Lai, Dongbing; Koller, Daniel L.; Huston, John; Broderick, Joseph P.

In: Stroke, Vol. 39, No. 5, 01.05.2008, p. 1434-1440.

Research output: Contribution to journalArticle

Foroud, T, Sauerbeck, L, Brown, R, Anderson, C, Woo, D, Kleindorfer, D, Flaherty, ML, Deka, R, Hornung, R, Meissner, I, Bailey-Wilson, JE, Rouleau, G, Connolly, ES, Lai, D, Koller, DL, Huston, J & Broderick, JP 2008, 'Genome screen to detect linkage to intracranial aneurysm susceptibility genes: The familial intracranial aneurysm (FIA) study', Stroke, vol. 39, no. 5, pp. 1434-1440. https://doi.org/10.1161/STROKEAHA.107.502930
Foroud, Tatiana ; Sauerbeck, Laura ; Brown, Robert ; Anderson, Craig ; Woo, Daniel ; Kleindorfer, Dawn ; Flaherty, Matthew L. ; Deka, Ranjan ; Hornung, Richard ; Meissner, Irene ; Bailey-Wilson, Joan E. ; Rouleau, Guy ; Connolly, E. Sander ; Lai, Dongbing ; Koller, Daniel L. ; Huston, John ; Broderick, Joseph P. / Genome screen to detect linkage to intracranial aneurysm susceptibility genes : The familial intracranial aneurysm (FIA) study. In: Stroke. 2008 ; Vol. 39, No. 5. pp. 1434-1440.
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AU - Anderson, Craig

AU - Woo, Daniel

AU - Kleindorfer, Dawn

AU - Flaherty, Matthew L.

AU - Deka, Ranjan

AU - Hornung, Richard

AU - Meissner, Irene

AU - Bailey-Wilson, Joan E.

AU - Rouleau, Guy

AU - Connolly, E. Sander

AU - Lai, Dongbing

AU - Koller, Daniel L.

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N2 - 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.

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