Browsing by Author "Meissner, Irene"

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    Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7
    (Ovid Technologies Wolters Kluwer – American Heart Association, 2014-11) Foroud, Tatiana; Lai, Dongbing; Koller, Daniel; van’t Hof, Femke; Kurki, Mitja I.; Anderson, Craig S.; Brown, Robert D.; Connolly, E. Sander; Eriksson, Johan G.; Flaherty, Matthew; Fornage, Myriam; von und zuFraunberg, Mikael; Gaál, Emília I.; Laakso, Aki; Hernesniemi, Juha; Huston, John; Jääskeläinen, Juha E.; Kiemeney, Lambertus A.; Kivisaari, Riku; Kleindorfer, Dawn; Ko, Nerissa; Lehto, Hanna; Mackey, Jason; Meissner, Irene; Moomaw, Charles J.; Mosley, Thomas H.; Moskala, Marek; Niemelä, Mika; Palotie, Aarno; Pera, Joanna; Rinkel, Gabriel; Ripke, Stephan; Rouleau, Guy; Ruigrok, Ynte; Sauerbeck, Laura; Słowik, Agnieszka; Vermeulen, Sita H.; Woo, Daniel; Worrall, Bradford B.; Broderick, Joseph; Department of Medical & Molecular Genetics, IU School of Medicine
    BACKGROUND AND PURPOSE: Common variants have been identified using genome-wide association studies which contribute to intracranial aneurysms (IA) susceptibility. However, it is clear that the variants identified to date do not account for the estimated genetic contribution to disease risk. METHODS: Initial analysis was performed in a discovery sample of 2617 IA cases and 2548 controls of white ancestry. Novel chromosomal regions meeting genome-wide significance were further tested for association in 2 independent replication samples: Dutch (717 cases; 3004 controls) and Finnish (799 cases; 2317 controls). A meta-analysis was performed to combine the results from the 3 studies for key chromosomal regions of interest. RESULTS: Genome-wide evidence of association was detected in the discovery sample on chromosome 9 (CDKN2BAS; rs10733376: P<1.0×10(-11)), in a gene previously associated with IA. A novel region on chromosome 7, near HDAC9, was associated with IA (rs10230207; P=4.14×10(-8)). This association replicated in the Dutch sample (P=0.01) but failed to show association in the Finnish sample (P=0.25). Meta-analysis results of the 3 cohorts reached statistical significant (P=9.91×10(-10)). CONCLUSIONS: We detected a novel region associated with IA susceptibility that was replicated in an independent Dutch sample. This region on chromosome 7 has been previously associated with ischemic stroke and the large vessel stroke occlusive subtype (including HDAC9), suggesting a possible genetic link between this stroke subtype and IA.
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    Screening for brain aneurysm in the Familial Intracranial Aneurysm study: frequency and predictors of lesion detection
    (Journal of Neurosurgery Publishing Group (JNSPG), 2008-06) Brown, Robert D., Jr.; Huston, John, III; Hornung, Richard; Foroud, Tatiana; Kallmes, David F.; Kleindorfer, Dawn; Meissner, Irene; Woo, Daniel; Sauerbeck, Laura; Broderick, Joseph; Department of Medical & Molecular Genetics, School of Medicine,
    Object Approximately 20% of patients with an intracranial saccular aneurysm report a family history of intracranial aneurysm (IA) or subarachnoid hemorrhage. A better understanding of predictors of aneurysm detection in familial IA may allow more targeted aneurysm screening strategies. Methods The Familial Intracranial Aneurysm (FIA) study is a multicenter study, in which the primary objective is to define the susceptibility genes related to the formation of IA. First-degree relatives (FDRs) of those affected with IA are offered screening with magnetic resonance (MR) angiography if they were previously unaffected, are ≥ 30 years of age, and have a history of smoking and/or hypertension. Independent predictors of aneurysm detection on MR angiography were determined using the generalized estimating equation version of logistic regression. Results Among the first 303 patients screened with MR angiography, 58 (19.1%) had at least 1 IA, including 24% of women and 11.7% of men. Ten (17.2%) of 58 affected patients had multiple aneurysms. Independent predictors of aneurysm detection included female sex (odds ratio [OR] 2.46, p = 0.001), pack-years of cigarette smoking (OR 3.24 for 20 pack-years of cigarette smoking compared with never having smoked, p < 0.001), and duration of hypertension (OR 1.26 comparing those with 10 years of hypertension to those with no hypertension, p = 0.006). Conclusions In the FIA study, among the affected patients’ FDRs who are > 30 years of age, those who are women or who have a history of smoking or hypertension are at increased risk of suffering an IA and should be strongly considered for screening.