Dataset Information

Common variants within oxidative phosphorylation genes influence risk of ischemic stroke and intracerebral hemorrhage.

ABSTRACT: BACKGROUND AND PURPOSE:Previous studies demonstrated association between mitochondrial DNA variants and ischemic stroke (IS). We investigated whether variants within a larger set of oxidative phosphorylation (OXPHOS) genes encoded by both autosomal and mitochondrial DNA were associated with risk of IS and, based on our results, extended our investigation to intracerebral hemorrhage (ICH). METHODS:This association study used a discovery cohort of 1643 individuals, a validation cohort of 2432 individuals for IS, and an extension cohort of 1476 individuals for ICH. Gene-set enrichment analysis was performed on all structural OXPHOS genes, as well as genes contributing to individual respiratory complexes. Gene-sets passing gene-set enrichment analysis were tested by constructing genetic scores using common variants residing within each gene. Associations between each variant and IS that emerged in the discovery cohort were examined in validation and extension cohorts. RESULTS:IS was associated with genetic risk scores in OXPHOS as a whole (odds ratio [OR], 1.17; P=0.008) and complex I (OR, 1.06; P=0.050). Among IS subtypes, small vessel stroke showed association with OXPHOS (OR, 1.16; P=0.007), complex I (OR, 1.13; P=0.027), and complex IV (OR, 1.14; P=0.018). To further explore this small vessel association, we extended our analysis to ICH, revealing association between deep hemispheric ICH and complex IV (OR, 1.08; P=0.008). CONCLUSIONS:This pathway analysis demonstrates association between common genetic variants within OXPHOS genes and stroke. The associations for small vessel stroke and deep ICH suggest that genetic variation in OXPHOS influences small vessel pathobiology. Further studies are needed to identify culprit genetic variants and assess their functional consequences.

SUBMITTER: Anderson CD

PROVIDER: S-EPMC3582722 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Common variants within oxidative phosphorylation genes influence risk of ischemic stroke and intracerebral hemorrhage.

Anderson Christopher D CD Biffi Alessandro A Nalls Michael A MA Devan William J WJ Schwab Kristin K Ayres Alison M AM Valant Valerie V Ross Owen A OA Rost Natalia S NS Saxena Richa R Viswanathan Anand A Worrall Bradford B BB Brott Thomas G TG Goldstein Joshua N JN Brown Devin D Broderick Joseph P JP Norrving Bo B Greenberg Steven M SM Silliman Scott L SL Hansen Björn M BM Tirschwell David L DL Lindgren Arne A Slowik Agnieszka A Schmidt Reinhold R Selim Magdy M Roquer Jaume J Montaner Joan J Singleton Andrew B AB Kidwell Chelsea S CS Woo Daniel D Furie Karen L KL Meschia James F JF Rosand Jonathan J

Stroke 20130129 3

<h4>Background and purpose</h4>Previous studies demonstrated association between mitochondrial DNA variants and ischemic stroke (IS). We investigated whether variants within a larger set of oxidative phosphorylation (OXPHOS) genes encoded by both autosomal and mitochondrial DNA were associated with risk of IS and, based on our results, extended our investigation to intracerebral hemorrhage (ICH).<h4>Methods</h4>This association study used a discovery cohort of 1643 individuals, a validation coho ...[more]

PMID: 23362085

Similar Datasets

Project description:Background Data on the relative contribution of clinical and neuroimaging risk factors to acute ischemic stroke (AIS) versus intracerebral hemorrhage (ICH) occurring on oral anticoagulant treatment are scarce. Methods and Results Cross-sectional study was done on consecutive oral anticoagulant-treated patients presenting with AIS, transient ischemic attack (TIA), or ICH from the prospective observational NOACISP (Novel-Oral-Anticoagulants-In-Stroke-Patients)-Acute registry. We compared clinical and neuroimaging characteristics (small vessel disease markers and atherosclerosis) in ICH versus AIS/TIA (reference) using logistic regression. Among 734 patients presenting with stroke on oral anticoagulant treatment (404 [55%] direct oral anticoagulants, 330 [45%] vitamin K antagonists), 605 patients (82%) had AIS/TIA and 129 (18%) had ICH. Prior AIS/TIA, coronary artery disease, dyslipidemia, and worse renal function were associated with AIS/TIA (adjusted odds ratio [aOR] [95% CI] 0.51 [0.32-0.82], 0.48 [0.26-0.86], 0.55 [0.34-0.89], and 0.82 [0.75-0.90] per 10 mL/min). Prior ICH, older age, higher admission blood pressure, and statin treatment were associated with ICH (aOR [95% CI] 6.33 [2.87-14.04], 1.37 [1.04-1.81] per 10 years, 1.19 [1.10-1.29] per 10 mm Hg, and 1.81 [1.09-3.03]). Cerebral microbleeds and moderate-to-severe white matter hyperintensities contributed more to ICH (aOR [95% CI] 2.77 [1.34-6.18], and 2.62 [1.28-5.63]). Aortic arch, common and internal carotid artery atherosclerosis, and internal carotid artery stenosis ≥50% contributed more to AIS/TIA (aOR [95% CI] 0.54 [0.31-0.90], 0.29 [0.05-0.97], 0.48 [0.30-0.76], and 0.32 [0.13-0.67]). Conclusions In patients presenting with stroke on oral anticoagulant, AIS/TIA was 5 times more common than ICH. A high atherosclerotic burden (indicated by cardiovascular comorbidities and extracranial atherosclerosis) and prior AIS/TIA contributed more to AIS/TIA, while small vessel disease markers and prior ICH were stronger determinants for ICH. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02353585.

Project description:BackgroundIntracerebral hemorrhage (ICH) is associated with an increased risk of ischemic stroke. Whether there are racial and ethnic disparities in the risk of ischemic stroke after ICH is poorly understood. We therefore aimed to test the hypothesis that non-Hispanic Black and Hispanic ICH patients have a higher risk of ischemic stroke compared with non-Hispanic White ICH patients.MethodsWe performed a retrospective cohort study using the Healthcare Cost and Utilization Project (HCUP) on all hospitalizations at all nonfederal hospitals in Florida from 2005 to 2018 and New York from 2006 to 2016. Race and ethnicity were coded as a single variable in HCUP. We included patients with an ICH, and without a prior or concomitant diagnosis of ischemic stroke, ascertained using validated International Classification of Diseases-Clinical Modification-9 and 10 diagnosis codes. Using Cox proportional hazard models, we studied the relationship between race and risk of ischemic stroke starting from the time of discharge from ICH hospitalization, after adjustment of demographics and vascular comorbidities.ResultsWe included 91 342 patients with ICH-62% non-Hispanic White, 18% non-Hispanic Black, and 12% Hispanic patients. Non-Hispanic Black and Hispanic patients were younger and had a higher prevalence of cardiovascular comorbidities; however, atrial fibrillation was more prevalent among non-Hispanic White patients. During a median follow-up period of 4.4 years (interquartile range, 1.5-8.1), an incident ischemic stroke occurred in 3377 (6%) non-Hispanic White, 1323 (8%) non-Hispanic Black, and 844 (8%) Hispanic patients. In adjusted Cox models, the risk of an ischemic stroke was significantly higher among non-Hispanic Black patients (hazard ratio, 1.6 [95% CI, 1.5-1.8]) and Hispanic patients (hazard ratio, 1.4 [95% CI, 1.3-1.5]), compared with non-Hispanic White patients. Similar results were obtained in sensitivity analyses when using death as a competing risk and after excluding patients with atrial fibrillation and valvular heart disease.ConclusionsIn a large heterogeneous cohort of patients with ICH, we found that non-Hispanic Black and Hispanic patients had a significantly higher risk of ischemic stroke compared with non-Hispanic White patients.

Dataset Information

Common variants within oxidative phosphorylation genes influence risk of ischemic stroke and intracerebral hemorrhage.

Publications

Common variants within oxidative phosphorylation genes influence risk of ischemic stroke and intracerebral hemorrhage.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets