Familial intracranial aneurysms: Is anatomic vulnerability heritable?

Jason Mackey, Robert D. Brown, Charles J. Moomaw, Richard Hornung, Laura Sauerbeck, Daniel Woo, Tatiana Foroud, Dheeraj Gandhi, Dawn Kleindorfer, Matthew L. Flaherty, Irene Meissner, Craig Anderson, Guy Rouleau, E. Sander Connolly, Ranjan Deka, Daniel L. Koller, Todd Abruzzo, John Huston, Joseph P. Broderick

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background and Purpose-: Previous studies have suggested that family members with intracranial aneurysms (IAs) often harbor IAs in similar anatomic locations. IA location is important because of its association with rupture. We tested the hypothesis that anatomic susceptibility to IA location exists using a family-based IA study. Methods-: We identified all affected probands and first-degree relatives (FDRs) with a definite or probable phenotype in each family. We stratified each IA of the probands by major arterial territory and calculated each family's proband-FDR territory concordance and overall contribution to the concordance analysis. We then matched each family unit to an unrelated family unit selected randomly with replacement and performed 1001 simulations. The median concordance proportions, odds ratios (ORs), and P values from the 1001 logistic regression analyses were used to represent the final results of the analysis. Results-: There were 323 family units available for analysis, including 323 probands and 448 FDRs, with a total of 1176 IAs. IA territorial concordance was higher in the internal carotid artery (55.4% versus 45.6%; OR, 1.54 [1.04-2.27]; P=0.032), middle cerebral artery (45.8% versus 30.5%; OR, 1.99 [1.22-3.22]; P=0.006), and vertebrobasilar system (26.6% versus 11.3%; OR, 2.90 [1.05-8.24], P=0.04) distributions in the true family compared with the comparison family. Concordance was also higher when any location was considered (53.0% versus 40.7%; OR, 1.82 [1.34-2.46]; P<0.001). Conclusions-: In a highly enriched sample with familial predisposition to IA development, we found that IA territorial concordance was higher when probands were compared with their own affected FDRs than with comparison FDRs, which suggests that anatomic vulnerability to IA formation exists. Future studies of IA genetics should consider stratifying cases by IA location.

Original languageEnglish
Pages (from-to)38-42
Number of pages5
JournalStroke
Volume44
Issue number1
DOIs
StatePublished - Jan 2013

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Intracranial Aneurysm
Odds Ratio
Middle Cerebral Artery
Internal Carotid Artery
Rupture
Logistic Models
Regression Analysis

Keywords

  • concordance
  • epidemiology
  • familial
  • genetics in stroke
  • heritability
  • intracranial aneurysm

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Clinical Neurology
  • Advanced and Specialized Nursing

Cite this

Mackey, J., Brown, R. D., Moomaw, C. J., Hornung, R., Sauerbeck, L., Woo, D., ... Broderick, J. P. (2013). Familial intracranial aneurysms: Is anatomic vulnerability heritable? Stroke, 44(1), 38-42. https://doi.org/10.1161/STROKEAHA.112.667261

Familial intracranial aneurysms : Is anatomic vulnerability heritable? / Mackey, Jason; Brown, Robert D.; Moomaw, Charles J.; Hornung, Richard; Sauerbeck, Laura; Woo, Daniel; Foroud, Tatiana; Gandhi, Dheeraj; Kleindorfer, Dawn; Flaherty, Matthew L.; Meissner, Irene; Anderson, Craig; Rouleau, Guy; Connolly, E. Sander; Deka, Ranjan; Koller, Daniel L.; Abruzzo, Todd; Huston, John; Broderick, Joseph P.

In: Stroke, Vol. 44, No. 1, 01.2013, p. 38-42.

Research output: Contribution to journalArticle

Mackey, J, Brown, RD, Moomaw, CJ, Hornung, R, Sauerbeck, L, Woo, D, Foroud, T, Gandhi, D, Kleindorfer, D, Flaherty, ML, Meissner, I, Anderson, C, Rouleau, G, Connolly, ES, Deka, R, Koller, DL, Abruzzo, T, Huston, J & Broderick, JP 2013, 'Familial intracranial aneurysms: Is anatomic vulnerability heritable?', Stroke, vol. 44, no. 1, pp. 38-42. https://doi.org/10.1161/STROKEAHA.112.667261
Mackey J, Brown RD, Moomaw CJ, Hornung R, Sauerbeck L, Woo D et al. Familial intracranial aneurysms: Is anatomic vulnerability heritable? Stroke. 2013 Jan;44(1):38-42. https://doi.org/10.1161/STROKEAHA.112.667261
Mackey, Jason ; Brown, Robert D. ; Moomaw, Charles J. ; Hornung, Richard ; Sauerbeck, Laura ; Woo, Daniel ; Foroud, Tatiana ; Gandhi, Dheeraj ; Kleindorfer, Dawn ; Flaherty, Matthew L. ; Meissner, Irene ; Anderson, Craig ; Rouleau, Guy ; Connolly, E. Sander ; Deka, Ranjan ; Koller, Daniel L. ; Abruzzo, Todd ; Huston, John ; Broderick, Joseph P. / Familial intracranial aneurysms : Is anatomic vulnerability heritable?. In: Stroke. 2013 ; Vol. 44, No. 1. pp. 38-42.
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AU - Woo, Daniel

AU - Foroud, Tatiana

AU - Gandhi, Dheeraj

AU - Kleindorfer, Dawn

AU - Flaherty, Matthew L.

AU - Meissner, Irene

AU - Anderson, Craig

AU - Rouleau, Guy

AU - Connolly, E. Sander

AU - Deka, Ranjan

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N2 - Background and Purpose-: Previous studies have suggested that family members with intracranial aneurysms (IAs) often harbor IAs in similar anatomic locations. IA location is important because of its association with rupture. We tested the hypothesis that anatomic susceptibility to IA location exists using a family-based IA study. Methods-: We identified all affected probands and first-degree relatives (FDRs) with a definite or probable phenotype in each family. We stratified each IA of the probands by major arterial territory and calculated each family's proband-FDR territory concordance and overall contribution to the concordance analysis. We then matched each family unit to an unrelated family unit selected randomly with replacement and performed 1001 simulations. The median concordance proportions, odds ratios (ORs), and P values from the 1001 logistic regression analyses were used to represent the final results of the analysis. Results-: There were 323 family units available for analysis, including 323 probands and 448 FDRs, with a total of 1176 IAs. IA territorial concordance was higher in the internal carotid artery (55.4% versus 45.6%; OR, 1.54 [1.04-2.27]; P=0.032), middle cerebral artery (45.8% versus 30.5%; OR, 1.99 [1.22-3.22]; P=0.006), and vertebrobasilar system (26.6% versus 11.3%; OR, 2.90 [1.05-8.24], P=0.04) distributions in the true family compared with the comparison family. Concordance was also higher when any location was considered (53.0% versus 40.7%; OR, 1.82 [1.34-2.46]; P<0.001). Conclusions-: In a highly enriched sample with familial predisposition to IA development, we found that IA territorial concordance was higher when probands were compared with their own affected FDRs than with comparison FDRs, which suggests that anatomic vulnerability to IA formation exists. Future studies of IA genetics should consider stratifying cases by IA location.

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