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  • Anderson, Christopher D. (author)

Common Variants Within Oxidative Phosphorylation Genes Influence Risk of Ischemic Stroke and Intracerebral Hemorrhage

  • Article/chapterEnglish2013

Publisher, publication year, extent ...

  • 2013

Numbers

  • LIBRIS-ID:oai:lup.lub.lu.se:77284986-1dc2-41d9-a84c-cd2e486f855f
  • https://lup.lub.lu.se/record/3657370URI
  • https://doi.org/10.1161/STROKEAHA.112.672089DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • 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. (Stroke. 2013;44:612-619.)

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Added entries (persons, corporate bodies, meetings, titles ...)

  • Biffi, Alessandro (author)
  • Nalls, Michael A. (author)
  • Devan, William J. (author)
  • Schwab, Kristin (author)
  • Ayres, Alison M. (author)
  • Valant, Valerie (author)
  • Ross, Owen A. (author)
  • Rost, Natalia S. (author)
  • Saxena, Richa (author)
  • Viswanathan, Anand (author)
  • Worrall, Bradford B. (author)
  • Brott, Thomas G. (author)
  • Goldstein, Joshua N. (author)
  • Brown, Devin (author)
  • Broderick, Joseph P. (author)
  • Norrving, BoLund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)neur-bno (author)
  • Greenberg, Steven M. (author)
  • Silliman, Scott L. (author)
  • Hansen, BjörnLund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-bhe (author)
  • Tirschwell, David L. (author)
  • Lindgren, ArneLund University,Lunds universitet,Neurologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Neurology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)neur-ali (author)
  • Slowik, Agnieszka (author)
  • Schmidt, Reinhold (author)
  • Selim, Magdy (author)
  • Roquer, Jaume (author)
  • Montaner, Joan (author)
  • Singleton, Andrew B. (author)
  • Kidwell, Chelsea S. (author)
  • Woo, Daniel (author)
  • Furie, Karen L. (author)
  • Meschia, James F. (author)
  • Rosand, Jonathan (author)
  • Neurologi, LundSektion IV (creator_code:org_t)

Related titles

  • In:Stroke: a journal of cerebral circulation44:3, s. 612-6191524-4628

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