Stroke. 2009 Jan;40(1):71-6. Epub 2008 Oct 23.
Genome screen to detect linkage to common susceptibility genes for intracranial and aortic aneurysms.
Worrall BB,
Foroud T,
Brown RD Jr,
Connolly ES,
Hornung RW,
Huston J 3rd,
Kleindorfer D,
Koller DL,
Lai D,
Moomaw CJ,
Sauerbeck L,
Woo D,
Broderick JP;
Familial Intracranial Aneurysm Study Investigators.
Ewing S, Sester J, Deka R, Foroud T, Koller D, Daubs M, Gray J, Kallmes D, Maronie Smith M, Fisher W, Forson H, Anderson C, Mee E, Howe C, Vos S, Hankey G, Knuckey N, Laidlaw J, Reilly P, Dorsch N, Morgan M, Besser M, Rosenfeld J, Athanasiadis K, Claxton A, Dunne V, Griffith J, Davidson J, Pope S, Froelich A, Day A, Brach R, Woo D, Zuccarello M, Ringer A, Yeh H, Franklin K, Ramussen P, Andrews-Hinders D, Wheeler T, Sacco R, LaMonica D, Lewis SB, Royster A, Payner T, Miracle N, Murphy K, Kohler B, Ogilvy C, Buckley D, Manansala J, Ferguson G, Mayer C, Peacock J, Rouleau G, Desjarlais A, Aldrich EF, Aldrich C, Byard C, Brown RD, Jaeger L, Morgenstern L, Concannon M, Qureshi AI, Harris P, Batjer H, Joven G, Thompson S, Richard MT, Hopper A, Kassam AB, Lee K, Johnston SC, Katsura K, Giannotta S, Fishback D, Steinberg G, Luu D, Coburn M, Malkoff M, Wojner A, Kassel NF, Worrall BB, Radakovic G, Tirschwell D, Tanzi P, Derdeyn C, Catanzaro M, Kaufmann A, Gladish D.
Source
University of Virginia Health System, Department of Neurology, Box 800394, Charlottesville, VA 22908, USA. bbw9r@virginia.edu
Erratum in
- Stroke. 2008 Dec;39(12):e195.
Abstract
BACKGROUND AND PURPOSE:
Risk for both intracranial aneurysms (IAs) and aortic aneurysms (AAs) is thought to be heritable with mounting evidence for genetic predisposition. The concept of shared risk for these conditions is challenged by differences in age of diagnosis and demographic characteristics. We performed a genomewide linkage analysis in multiplex families with both IA and AA from the Familial Intracranial Aneurysm study.
METHODS:
Available medical records of subjects who reported IA or abdominal/thoracic AA were reviewed with adjudication as definite/probable, possible, or not a case. To identify genes contributing to the susceptibility for IA and AA, genomewide linkage analysis was performed in the 26 multiplex IA families who had members who also had thoracic or abdominal AA. Individuals (n=91) were defined as affected if they had an IA (definite/probable) or an aortic or thoracic AA (definite/probable).
RESULTS:
Maximum logarithm of odds (LOD) scores were found on chromosomes 11 (144 cM; LOD=3.0) and 6 (33 cM; LOD=2.3). In both chromosomal regions, analyses of these same 26 families considering only IA as the disease phenotype produced LOD scores of 1.8 and 1.6, respectively.
CONCLUSIONS:
Our linkage analysis in these 26 families using the broadest disease phenotype, including IA, abdominal AA, and thoracic AA, supports the concept of shared genetic risk. The chromosome 11 locus appears to confirm earlier independent associations in IA and AA. The chromosome 6 finding is novel. Both warrant further investigation.
- PMID:
- 18948608
- [PubMed - indexed for MEDLINE]
- PMCID:
- PMC2629798
Free PMC ArticleFigure
Results of multipoint, model independent linkage analysis. A, Broadest disease definition: IA, AAA, or TAA. B, IA alone in the same families. C, Restricted disease definition: IA or TAA.
Stroke. Stroke;40(1):71-76.
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