好色先生

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Abstract Details

Common Variants within Oxidative Phosphorylation Genes Influence Risk of Ischemic Stroke and Intracerebral Hemorrhage
Cerebrovascular Disease and Interventional Neurology
S41 - (-)
002
Mitochondrial disorders caused by poor OXPHOS function result in neurologic phenotypes including stroke and encephalopathy. Defects within each of the five OXPHOS Complexes cause human disease. Prior research demonstrated association between mitochondrial DNA variants and IS, but the majority of OXPHOS proteins are encoded by the nuclear genome.
This multi-center association study employed an IS discovery cohort of 1643 individuals, an IS validation cohort of 2432 individuals, and an ICH extension cohort of 1476 individuals. OXPHOS common variants within the nuclear and mitochondrial genomes were included. Separate analyses were performed for IS and ICH subtypes. Gene-set enrichment analysis (GSEA) was performed on all OXPHOS genes, as well as genes contributing to individual OXPHOS Complexes. Gene-sets passing GSEA 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.
In our replication cohort, 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 (SV) 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). In the ICH extension cohort, an association was found between deep hemispheric ICH and Complex IV (OR=1.08, p=0.008).
This pathway analysis demonstrates associations between common genetic variants within OXPHOS genes and stroke. The associations for SV stroke and deep ICH suggest that genetic variation in OXPHOS may influence small vessel pathobiology. Further studies are needed to identify culprit genetic variants and assess their functional consequences.
Authors/Disclosures
Christopher D. Anderson, MD, PhD, FAAN (Brigham and Women's Hospital)
PRESENTER 		The institution of Dr. Anderson has received research support from Bayer AG. The institution of Dr. Anderson has received research support from American Heart Association. The institution of Dr. Anderson has received research support from National Institutes of Health. An immediate family member of Dr. Anderson has received publishing royalties from a publication relating to health care.
Alessandro Biffi, MD (Eli Lilly and Company) Dr. Biffi has received personal compensation for serving as an employee of Eli Lilly And Company. Dr. Biffi has stock in Eli Lilly And Company.
No disclosure on file
No disclosure on file
No disclosure on file
Kristin Schwab No disclosure on file
No disclosure on file
No disclosure on file
Owen A. Ross, PhD (Mayo Clinic Jacksonville) Dr. Ross has nothing to disclose.
Natalia S. Rost, MD, MPH, FAAN, FAHA (Massachusetts General Hospital) Dr. Rost has received personal compensation in the range of $50,000-$99,999 for serving as an officer or member of the Board of Directors for 好色先生. Dr. Rost has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Stroke - AHA/ASA Journal. The institution of Dr. Rost has received research support from NIH. Dr. Rost has received publishing royalties from a publication relating to health care.
No disclosure on file
Anand Viswanathan, MD (Massachusetts General Hospital) Dr. Viswanathan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alnylam Pharmaceuticals. Dr. Viswanathan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Viswanathan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche Pharmaceuticals.
Bradford B. Worrall, MD, MSc, FAAN (University Of Virginia Health System) The institution of Dr. Worrall has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. The institution of Dr. Worrall has received research support from NIH.
Thomas G. Brott, MD, FAAN (Mayo Clinic) Dr. Brott has nothing to disclose.
Joshua Goldstein (Massachusetts General Hospital) Joshua Goldstein has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CSL Behring. The institution of Joshua Goldstein has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octapharma. Joshua Goldstein has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astrazeneca. The institution of Joshua Goldstein has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. The institution of Joshua Goldstein has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Octapharma. Joshua Goldstein has stock in NControl. Joshua Goldstein has stock in Cayuga. The institution of Joshua Goldstein has received research support from Pfizer. The institution of Joshua Goldstein has received research support from Takeda.
Devin L. Brown, MD, FAAN (CVC) The institution of Dr. Brown has received research support from NIH.
Joseph P. Broderick, MD, FAAN (University of Cincinnati) Dr. Broderick has received publishing royalties from a publication relating to health care.
No disclosure on file
Steven M. Greenberg, MD, PhD, FAAN Dr. Greenberg has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer. Dr. Greenberg has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squib. The institution of Dr. Greenberg has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alnylam. Dr. Greenberg has received research support from National Institutes of Health. Dr. Greenberg has received publishing royalties from a publication relating to health care.
Scott L. Silliman, MD (U.F. College of Medicine-Jacksonville) Dr. Silliman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech.
No disclosure on file
David L. Tirschwell, MD, FAAN (Harborview Medical Center) Dr. Tirschwell has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for CARMAT. Dr. Tirschwell has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AbbVie. The institution of Dr. Tirschwell has received research support from Abbott. The institution of Dr. Tirschwell has received research support from NIH.
No disclosure on file
Agnieszka Slowik, MD, FAAN (Jagiellonian University) Dr. Slowik has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Boehringer, . Dr. Slowik has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Slowik has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis.
Reinhold Schmidt, MD No disclosure on file
Magdy H. Selim, MD, PhD (Beth Israel Deaconess Med. Ctr.) Dr. Selim has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MedRhythms Inc..
Jaume Roquer Gonzalez (Hospital Del Mar) No disclosure on file
No disclosure on file
Andrew Singleton An immediate family member of Andrew Singleton has received personal compensation for serving as an employee of GeneDx. Andrew Singleton has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Nature Partner Journals Parkinson Disease. Andrew Singleton has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Movement Disorders Journal. An immediate family member of Andrew Singleton has stock in GeneDx. The institution of Andrew Singleton has received research support from Michael J Fox Foundation. Andrew Singleton has received intellectual property interests from a discovery or technology relating to health care. Andrew Singleton has received intellectual property interests from a discovery or technology relating to health care.
Chelsea S. Kidwell, MD (University of Arizona Department of Neurology) No disclosure on file
Daniel Woo, MD, FAAN (University at Buffalo) The institution of Dr. Woo has received research support from NIH.
Karen L. Furie, MD (RIH/Alpert Medical School of Brown Univ) The institution of Dr. Furie has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen/BMS. Dr. Furie has received personal compensation in the range of $50,000-$99,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for BMJ/JNNP. The institution of Dr. Furie has received research support from NINDS.
James F. Meschia, MD, FAAN (Mayo Clinic) The institution of Dr. Meschia has received research support from NINDS. The institution of Dr. Meschia has received research support from NINDS.
Jonathan Rosand, MD (Massachusetts General Hospital) Dr. Rosand has received personal compensation for serving as an employee of Massachusetts General Hospital. Dr. Rosand has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eli Lilly and Co. Dr. Rosand has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Rosand has received personal compensation in the range of $50,000-$99,999 for serving as an Expert Witness for National Football League. The institution of Dr. Rosand has received research support from NIH. The institution of Dr. Rosand has received research support from American Heart Association. Dr. Rosand has received personal compensation in the range of $0-$499 for serving as a Peer reviewer with National Institutes of Health. Dr. Rosand has a non-compensated relationship as a Trustee with Columbia University that is relevant to AAN interests or activities.