Browsing by Author "Anderson, Craig"

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    Genome-Wide Association Study of Intracranial Aneurysms Confirms Role of Anril and SOX17 in Disease Risk
    (American Heart Association, 2012) Foroud, Tatiana; Koller, Daniel L.; Lai, Dongbing; Sauerbeck, Laura; Anderson, Craig; Ko, Nerissa; Deka, Ranjan; Mosley, Thomas H.; Fornage, Myriam; Woo, Daniel; Moomaw, Charles J.; Hornung, Richard; Huston, John; Meissner, Irene; Bailey-Wilson, Joan E.; Langefeld, Carl; Rouleau, Guy; Connolly, E. Sander; Worrall, Bradford B.; Kleindorfer, Dawn; Flaherty, Matthew L.; Martini, Sharyl; Mackey, Jason; De Los Rios La Rosa, Felipe; Brown, Robert D., Jr.; Broderick, Joseph P.; FIA Study Investigators; Medical and Molecular Genetics, School of Medicine
    Background: Genomewide association studies have identified novel genetic factors that contribute to intracranial aneurysm (IA) susceptibility. We sought to confirm previously reported loci, to identify novel risk factors, and to evaluate the contribution of these factors to familial and sporadic IA. Method: We utilized 2 complementary samples, one recruited on the basis of a dense family history of IA (discovery sample 1: 388 IA cases and 397 controls) and the other without regard to family history (discovery sample 2: 1095 IA cases and 1286 controls). Imputation was used to generate a common set of single nucleotide polymorphisms (SNP) across samples, and a logistic regression model was used to test for association in each sample. Results from each sample were then combined in a metaanalysis. Results: There was only modest overlap in the association results obtained in the 2 samples. In neither sample did results reach genomewide significance. However, the metaanalysis yielded genomewide significance for SNP on chromosome 9p (CDKN2BAS; rs6475606; P=3.6×10(-8)) and provided further evidence to support the previously reported association of IA with SNP in SOX17 on chromosome 8q (rs1072737; P=8.7×10(-5)). Analyses suggest that the effect of smoking acts multiplicatively with the SNP genotype, and smoking has a greater effect on risk than SNP genotype. Conclusions: In addition to replicating several previously reported loci, we provide further evidence that the association on chromosome 9p is attributable to variants in CDKN2BAS (also known as ANRIL, an antisense noncoding RNA).
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    Unruptured intracranial aneurysms in the Familial Intracranial Aneurysm and International Study of Unruptured Intracranial Aneurysms cohorts: differences in multiplicity and location
    (American Association of Neurological Surgeons, 2012) Mackey, Jason; Brown, Robert D., Jr.; Moomaw, Charles J.; Sauerbeck, Laura; Hornung, Richard; Gandhi, Dheeraj; Woo, Daniel; Kleindorfer, Dawn; Flaherty, Matthew L.; Meissner, Irene; Anderson, Craig; Connolly, E. Sander; Rouleau, Guy; Kallmes, David F.; Torner, James; Huston, John, III; Broderick, Joseph P.; Neurology, School of Medicine
    Object: Familial predisposition is a recognized nonmodifiable risk factor for the formation and rupture of intracranial aneurysms (IAs). However, data regarding the characteristics of familial IAs are limited. The authors sought to describe familial IAs more fully, and to compare their characteristics with a large cohort of nonfamilial IAs. Methods: The Familial Intracranial Aneurysm (FIA) study is a multicenter international study with the goal of identifying genetic and other risk factors for formation and rupture of IAs in a highly enriched population. The authors compared the FIA study cohort with the International Study of Unruptured Intracranial Aneurysms (ISUIA) cohort with regard to patient demographic data, IA location, and IA multiplicity. To improve comparability, all patients in the ISUIA who had a family history of IAs or subarachnoid hemorrhage were excluded, as well as all patients in both cohorts who had a ruptured IA prior to study entry. Results: Of 983 patients enrolled in the FIA study with definite or probable IAs, 511 met the inclusion criteria for this analysis. Of the 4059 patients in the ISUIA study, 983 had a previous IA rupture and 657 of the remainder had a positive family history, leaving 2419 individuals in the analysis. Multiplicity was more common in the FIA patients (35.6% vs 27.9%, p<0.001). The FIA patients had a higher proportion of IAs located in the middle cerebral artery (28.6% vs 24.9%), whereas ISUIA patients had a higher proportion of posterior communicating artery IAs (13.7% vs 8.2%, p=0.016). Conclusions: Heritable structural vulnerability may account for differences in IA multiplicity and location. Important investigations into the underlying genetic mechanisms of IA formation are ongoing.