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

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Fältnamn	Indikatorer	Metadata
000		05056naa a2200709 4500
001		oai:lup.lub.lu.se:77284986-1dc2-41d9-a84c-cd2e486f855f
003		SwePub
008		160401s2013 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://lup.lub.lu.se/record/36573702 URI
024	7	a https://doi.org/10.1161/STROKEAHA.112.6720892 DOI
040		a (SwePub)lu
041		a engb eng
042		9 SwePub
072	7	a art2 swepub-publicationtype
072	7	a ref2 swepub-contenttype
100	1	a Anderson, Christopher D.4 aut
245	1 0	a Common Variants Within Oxidative Phosphorylation Genes Influence Risk of Ischemic Stroke and Intracerebral Hemorrhage
264	1	c 2013
520		a 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.)
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Neurologi0 (SwePub)302072 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Neurology0 (SwePub)302072 hsv//eng
653		a genes
653		a mitochondria
653		a OXPHOS
653		a stroke
700	1	a Biffi, Alessandro4 aut
700	1	a Nalls, Michael A.4 aut
700	1	a Devan, William J.4 aut
700	1	a Schwab, Kristin4 aut
700	1	a Ayres, Alison M.4 aut
700	1	a Valant, Valerie4 aut
700	1	a Ross, Owen A.4 aut
700	1	a Rost, Natalia S.4 aut
700	1	a Saxena, Richa4 aut
700	1	a Viswanathan, Anand4 aut
700	1	a Worrall, Bradford B.4 aut
700	1	a Brott, Thomas G.4 aut
700	1	a Goldstein, Joshua N.4 aut
700	1	a Brown, Devin4 aut
700	1	a Broderick, Joseph P.4 aut
700	1	a Norrving, Bou Lund 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 Medicine4 aut0 (Swepub:lu)neur-bno
700	1	a Greenberg, Steven M.4 aut
700	1	a Silliman, Scott L.4 aut
700	1	a Hansen, Björnu Lund 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 Medicine4 aut0 (Swepub:lu)med-bhe
700	1	a Tirschwell, David L.4 aut
700	1	a Lindgren, Arneu Lund 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 Medicine4 aut0 (Swepub:lu)neur-ali
700	1	a Slowik, Agnieszka4 aut
700	1	a Schmidt, Reinhold4 aut
700	1	a Selim, Magdy4 aut
700	1	a Roquer, Jaume4 aut
700	1	a Montaner, Joan4 aut
700	1	a Singleton, Andrew B.4 aut
700	1	a Kidwell, Chelsea S.4 aut
700	1	a Woo, Daniel4 aut
700	1	a Furie, Karen L.4 aut
700	1	a Meschia, James F.4 aut
700	1	a Rosand, Jonathan4 aut
710	2	a Neurologi, Lundb Sektion IV4 org
773	0	t Stroke: a journal of cerebral circulationg 44:3, s. 612-619q 44:3<612-619x 1524-4628
856	4	u http://dx.doi.org/10.1161/STROKEAHA.112.672089y FULLTEXT
856	4 8	u https://lup.lub.lu.se/record/3657370
856	4 8	u https://doi.org/10.1161/STROKEAHA.112.672089

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