Genome screen in familial intracranial aneurysm.

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, Carl Langefeld, Guy Rouleau, E. Sander Connolly, Dongbing Lai, Daniel L. Koller, John Huston, Joseph P. Broderick

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

BACKGROUND: Individuals with 1st degree relatives harboring an intracranial aneurysm (IA) are at an increased risk of IA, suggesting genetic variation is an important risk factor. METHODS: Families with multiple members having ruptured or unruptured IA were recruited and all available medical records and imaging data were reviewed to classify possible IA subjects as definite, probable or possible IA or not a case. A 6 K SNP genome screen was performed in 333 families, representing the largest linkage study of IA reported to date. A 'narrow' (n = 705 definite IA cases) and 'broad' (n = 866 definite or probable IA) disease definition were used in multipoint model-free linkage analysis and parametric linkage analysis, maximizing disease parameters. Ordered subset analysis (OSA) was used to detect gene x smoking interaction. RESULTS: Model-free linkage analyses detected modest evidence of possible linkage (all LOD < 1.5). Parametric analyses yielded an unadjusted LOD score of 2.6 on chromosome 4q (162 cM) and 3.1 on chromosome 12p (50 cM). Significant evidence for a gene x smoking interaction was detected using both disease models on chromosome 7p (60 cM; p </= 0.01). Our study provides modest evidence of possible linkage to several chromosomes. CONCLUSION: These data suggest it is unlikely that there is a single common variant with a strong effect in the majority of the IA families. Rather, it is likely that multiple genetic and environmental risk factors contribute to the susceptibility for intracranial aneurysms.

Original languageEnglish
Pages (from-to)3
Number of pages1
JournalBMC Medical Genetics
Volume10
DOIs
StatePublished - 2009

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Intracranial Aneurysm
Genome
Chromosomes
Smoking
Diagnostic Imaging
Genes
Medical Records
Single Nucleotide Polymorphism

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Foroud, T., Sauerbeck, L., Brown, R., Anderson, C., Woo, D., Kleindorfer, D., ... Broderick, J. P. (2009). Genome screen in familial intracranial aneurysm. BMC Medical Genetics, 10, 3. https://doi.org/10.1186/1471-2350-10-3

Genome screen in familial intracranial aneurysm. / 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.; Langefeld, Carl; Rouleau, Guy; Connolly, E. Sander; Lai, Dongbing; Koller, Daniel L.; Huston, John; Broderick, Joseph P.

In: BMC Medical Genetics, Vol. 10, 2009, p. 3.

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, Langefeld, C, Rouleau, G, Connolly, ES, Lai, D, Koller, DL, Huston, J & Broderick, JP 2009, 'Genome screen in familial intracranial aneurysm.', BMC Medical Genetics, vol. 10, pp. 3. https://doi.org/10.1186/1471-2350-10-3
Foroud T, Sauerbeck L, Brown R, Anderson C, Woo D, Kleindorfer D et al. Genome screen in familial intracranial aneurysm. BMC Medical Genetics. 2009;10:3. https://doi.org/10.1186/1471-2350-10-3
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. ; Langefeld, Carl ; Rouleau, Guy ; Connolly, E. Sander ; Lai, Dongbing ; Koller, Daniel L. ; Huston, John ; Broderick, Joseph P. / Genome screen in familial intracranial aneurysm. In: BMC Medical Genetics. 2009 ; Vol. 10. pp. 3.
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AU - Anderson, Craig

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AU - Flaherty, Matthew L.

AU - Deka, Ranjan

AU - Hornung, Richard

AU - Meissner, Irene

AU - Bailey-Wilson, Joan E.

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AU - Huston, John

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