on October 30, 2008
Published online before print October 23, 2008, doi: 10.1161/STROKEAHA.108.522631
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Submitted on May 8, 2008
From the Departments of Neurology and Public Health Sciences (B.B.W.), University of Virginia, Charlottesville, Va; the Department of Medical and Molecular Genetics (T.F., D.L.K., D.L.), Indiana University School of Medicine, Indianapolis, Ind; the Departments of Neurology (R.D.B.) and Radiology (J.H.), Mayo Clinic, Rochester, Minn; the Department of Neurological Surgery (E.S.C.), Columbia University, New York, NY; the Departments of Pediatrics and Environmental Health (R.W.H.), Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; and the Department of Neurology (D.K., C.J.M., L.S., D.W., J.P.B.), University of Cincinnati College of Medicine, Cincinnati, Ohio. * To whom correspondence should be addressed. E-mail: bbw9r{at}virginia.edu.
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.
Accepted on June 3, 2008
Genome Screen to Detect Linkage to Common Susceptibility Genes for Intracranial and Aortic Aneurysms
Bradford B. Worrall MD, MSc*;
Key words: aortic aneurysms • genetic linkage • genetic susceptibility • intracranial aneurysm • single nucleotide polymorphism