Journal article
Genome screen in familial intracranial aneurysm
BMC medical genetics, Vol.10(1), pp.3-3
2009
DOI: 10.1186/1471-2350-10-3
PMCID: PMC2636777
PMID: 19144135
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.
Details
- Title: Subtitle
- Genome screen in familial intracranial aneurysm
- Creators
- Tatiana Foroud - Indiana University School of Medicine, Indianapolis, IN, USALaura Sauerbeck - University of Cincinnati School of Medicine, Cincinnati, OH, USARobert Brown - Mayo Clinic, Rochester, MN, USACraig Anderson - The George Institute for International Health, University of Sydney, Sydney, AustraliaDaniel Woo - University of Cincinnati School of Medicine, Cincinnati, OH, USADawn Kleindorfer - University of Cincinnati School of Medicine, Cincinnati, OH, USAMatthew L Flaherty - University of Cincinnati School of Medicine, Cincinnati, OH, USARanjan Deka - University of Cincinnati School of Medicine, Cincinnati, OH, USARichard Hornung - Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USAIrene Meissner - Mayo Clinic, Rochester, MN, USAJoan E Bailey-Wilson - National Human Genome Research Institute, Baltimore, MD, USACarl Langefeld - Wake Forest University of Medicine, Winston-Salem, NC, USAGuy Rouleau - Center of Excellence in Neuromics, University of Montreal, Montreal, CanadaE Sander Connolly - Columbia University, New York, NY, USADongbing Lai - Indiana University School of Medicine, Indianapolis, IN, USADaniel L Koller - Indiana University School of Medicine, Indianapolis, IN, USAJohn Huston III - Mayo Clinic, Rochester, MN, USAJoseph P Broderick - University of Cincinnati School of Medicine, Cincinnati, OH, USAFamilial Intracranial Aneurysm Study Investigators
- Contributors
- Colin P Derdeyn (Contributor) - University of Iowa, Radiology
- Resource Type
- Journal article
- Publication Details
- BMC medical genetics, Vol.10(1), pp.3-3
- DOI
- 10.1186/1471-2350-10-3
- PMID
- 19144135
- PMCID
- PMC2636777
- NLM abbreviation
- BMC Med Genet
- ISSN
- 1471-2350
- eISSN
- 1471-2350
- Publisher
- BioMed Central
- Language
- English
- Date published
- 2009
- Academic Unit
- Neurology; Radiology; Iowa Neuroscience Institute; Neurosurgery
- Record Identifier
- 9984014021102771
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