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Browsing by Author "Anderson, Craig S."
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Item 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 MedicineBACKGROUND 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.Item Sleep for Stroke Management and Recovery Trial (Sleep SMART): Rationale and methods(Sage, 2020-10) Brown, Devin L.; Durkalski, Valerie; Durmer, Jeffrey S.; Broderick, Joseph P.; Zahuranec, Darin B.; Levine, Deborah A.; Anderson, Craig S.; Bravata, Dawn M.; Yaggi, H. Klar; Morgenstern, Lewis B.; Moy, Claudia S.; Chervin, Ronald D.; Neurology, School of MedicineRationale: Obstructive sleep apnea is common among patients with acute ischemic stroke and is associated with reduced functional recovery and an increased risk for recurrent vascular events. Aims and/or hypothesis: The Sleep for Stroke Management and Recovery Trial (Sleep SMART) aims to determine whether automatically adjusting continuous positive airway pressure (aCPAP) treatment for obstructive sleep apnea improves clinical outcomes after acute ischemic stroke or high-risk transient ischemic attack. Sample size estimate: A total of 3062 randomized subjects for the prevention of recurrent serious vascular events, and among these, 1362 stroke survivors for the recovery outcome. Methods and design: Sleep SMART is a phase III, multicenter, prospective randomized, open, blinded outcome event assessed controlled trial. Adults with recent acute ischemic stroke/transient ischemic attack and no contraindication to aCPAP are screened for obstructive sleep apnea with a portable sleep apnea test. Subjects with confirmed obstructive sleep apnea but without predominant central sleep apnea proceed to a run-in night of aCPAP. Subjects with use (≥4 h) of aCPAP and without development of significant central apneas are randomized to aCPAP plus usual care or care-as-usual for six months. Telemedicine is used to monitor and facilitate aCPAP adherence remotely. Study outcomes: Two separate primary outcomes: (1) the composite of recurrent acute ischemic stroke, acute coronary syndrome, and all-cause mortality (prevention) and (2) the modified Rankin scale scores (recovery) at six- and three-month post-randomization, respectively. Discussion: Sleep SMART represents the first large trial to test whether aCPAP for obstructive sleep apnea after stroke/transient ischemic attack reduces recurrent vascular events or death, and improves functional recovery.