Common Genetic Variation in Relation to Brachial Vascular Dimensions and Flow-Mediated Vasodilation
Year: 2019
Type: article
Abstract: rachial artery dimensions and reactivity as assessed by flow-mediated dilation (FMD) using ultrasound have been associated with cardiovascular disease. 1 Systematic analysis of common genetic variation and brachial artery reactivity may help explain the hereditary component of vascular function.2 We performed an inverse variance weighting in a fixed effects meta-analysis of 6 genome-wide association studies on brachial artery diameter, maximum brachial artery diameter adjusted for baseline diameter, and FMD totaling 17 151 community-based individuals of European ancestry (Cardiovascular Health Study, Framingham Heart Study, GHS (Gutenberg Health Study), Prospective Investigation of the Vasculature in Uppsala Seniors, SHIP (Study of Health in Pomerania), and Young Finns Study).For replication, we genotyped up to 9555 independent individuals of the GHS using functionally tested standard 5´ nuclease assays on a 7900HT Fast Real-Time polymerase chain reaction system (Applied Biosystems).We selected 8 single nucleotide polymorphisms (SNPs; 6 for brachial artery diameter, 2 for maximum brachial artery diameter adjusted for baseline diameter, and 0 for FMD) with genome-wide significance or nominally significant regions with several supporting signals in the region and pathophysiological plausibility for replication by de novo genotyping in an independent GHS sample.Furthermore, we performed a stage 2 meta-analysis including all individuals.All studies were approved by the local ethics committees.Because of the sensitive nature of the data collected for this study, requests to access the dataset from qualified researchers trained in human subject confidentiality protocols may be sent to Dr med.Renate B. Schnabel at Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf,
Authors: Marcus Dörr, Naomi M. Hamburg, Christian Müller, Nicholas L. Smith, Stefan Gustafsson, Terho Lehtimäki, Alexander Teumer, Tanja Zeller, Xiaohui Li, Lars Lind, Olli T. Raitakari, Uwe Völker, Stefan Blankenberg, Barbara McKnight, Andrew P. Morris, Mika Kähönen, Rozenn N. Lemaitre, Philipp S. Wild, Matthias Nauck, Henry Völzke, Thomas Münzel, Gary F. Mitchell, Bruce M Psaty, Cecilia M. Lindgren, Martin G. Larson, Stephan B. Felix, Erik Ingelsson, Leo-Pekka Lyytikäinen, David Herrington, Emelia J. Benjamin, Renate B Schnabel
Institutions: Universitätsmedizin Greifswald, Universität Greifswald, German Centre for Cardiovascular Research, Boston University, University Medical Center Hamburg-Eppendorf, Kaiser Permanente Washington Health Research Institute, University of Washington, VA Office of Research and Development, Seattle Epidemiologic Information and Research Center, Uppsala University, Science for Life Laboratory, Tampere University, Fimlab (Finland), University of Tampere, The Lundquist Institute, Harbor–UCLA Medical Center, University of Turku, Turku University Hospital, University of Liverpool, Tampere University Hospital, Johannes Gutenberg University Mainz, University Medical Center of the Johannes Gutenberg University Mainz, Broad Institute, Centre for Human Genetics, Harvard University, University of Oxford, Massachusetts Institute of Technology, National Heart, Lung, and Blood Institute, Framingham Heart Study, Stanford Medicine, Stanford Diabetes Research Center, Stanford Cardiovascular Institute, Stanford University, Wake Forest University Health Sciences, Wake Forest University
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Massachusetts Institute of Technology, Wake Forest University, Harvard University, School of Medicine, Boston University, Foundation for Cardiovascular Research, Yrjö Jahnssonin Säätiö, Wellcome Trust, Deutsches Zentrum für Herz-Kreislaufforschung, Broad Institute, Stanford Diabetes Research Center, University of Oxford, European Commission, Deutsche Forschungsgemeinschaft, Kela, Academy of Finland, Bundesministerium für Bildung und Forschung, Suomen Kulttuurirahasto, Juho Vainion Säätiö, Signe ja Ane Gyllenbergin Säätiö, Stiftung Rheinland-Pfalz für Innovation, Tampereen Yliopisto, Emil Aaltosen Säätiö, Siemens, Sydäntutkimussäätiö, Tampereen Tuberkuloosisäätiö, Diabetesliitto, Paavo Nurmen Säätiö, Tays, Universität Greifswald, Ministry of Cultural Affairs, National Institutes of Health, School of Medicine, Stanford University, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Stanford Cardiovascular Institute, School of Medicine, Stanford University, H2020 European Research Council
Awards: G1023702118, G1028935811, G1097528416, G1154816807, Juniorverbünde in der Systemmedizin: Molekulare Charakterisierung von Kandidatengenen und Signalwegen für das Vorhofflimmern sowie Untersuchungen zur Genetischen Epidemiologie (symAtrial), Universitätsklinkum Hamburg-Epppendorf, G1220223050, G125972088, CORONARY HEART DISEASE AND STROKE, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G1322015900, G1332411685, G1335418636, G1401438683, G1438302022, G1476847741, G1518085888, G1601895641, CORONARY HEART DISEASE AND STROKE, G1696540499, G1726490033, G1872575776, Ancestral environmental exposures and offspring health – a multigenerational epidemiologic cohort study across 3 generations, G1890882945, G1891033315, G2026946236, Rare variants and NHLBI traits in deeply phenotyped cohorts, G2194386449, G2230772921, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, Verbundprojekt: Spitzenforschung und Innovation in den Neuen Ländern - GANI_MED - Greifswald Approach to Individualized Medicine, G232264632, G2330237237, G2391884931, G2404385439, G247538147, G250621538, G2540648404, CORONARY HEART DISEASE &STROKE IN THE ELDERLY, G2634934472, G270907595, G2751623847, G27566159, A multidisciplinary approach for the stratification of patients with carotid artery disease, G278200998, G2800149121, G2899267414, G297113894, G3007488127, G3013445753, G3045517347, WGA Study to Identify Genetic Variants Associated with CV Events in CHS, G3111916513, G3137375862, Prospective meta-analyses of drug-gene interactions: CHARGE GWAS consortium, G3213590351, G3220743633, G322252321, G3230097750, UCLA Clinical and Translational Science Institute, G3283323707, G33539551, G3405256882, G34347772, CHS research resources for the cardiovascular health of older adults, AFGen Consortium: Atrial Fibrillation Genomics to Functional Analyses, G3582688621, G3692229207, G3858258543, G3868930229, Decision making and augmented reality support for automatic welding installations, CENTRAL BLOOD ANALYSIS LABORATORY FOR CHS, Genetics and genomics of central obesity ., G4094304602, G4139205196, G4219624527, G423252844, G4321089066, G434337789, G4429312988, Aging and Inflammation: Longitudinal Markers and Genetics in the Framingham Study, G4622379297, G4655867613, G472208673, G475755283, Anwendung von DNA-Array-Technologien in Molekularer Medizin und Mikrobiologie, G4764896896, Centrum für Thrombose und Hämostase (CTH) Mainz, G4942589162, G4965406020, Verbesserung der Leistungsfähigkeit der klinischen Forschung besonders in den Schwerpunkten Community Medicine und Molekulare Medizin, Phase II, G512922464, G5145575165, G5164707915, G5165178750, G5208171454, G5233356934, G5251985303, G5439707361, G544148272, G5479317095, G5678199996, G5713454673, G5770909501, G581887176, G5822176667, CHS Events Follow-up Study, G6015547599, G6029994567, Framingham: Inflammation, Genes & Cardiovascular Disease, G6226795708, G6355767702, G6413504379, The Framingham Heart Study, G6706757010, G6802942620, G6822215221, G7007046788, G716312657, G7176672723, G7217924807, G7244861316, G7453583093, Vascular Function in the Framingham Third Generation, G7558636403, G764651519, G766700449, G766843672, G7766767256, G7885066867, G8043620596, G806768229, G8068269535, G8073265216, G8260701975, G8399513454, G844559411, G8492131798, CHS-Transition Phase -268055222, G8683204365, Verbesserung der Struktur- und Leistungsfähigkeit der klinischen Forschung besonders in den Schwerpunkten Community Medicine und Molekulare Medizin, G8892155751, G9000026278, G9000027259, G9000046001, G9000069887, G9000071222, G9000085589, G9000124008, G9000124674, G9000139054, G9000140433, G9000144594, G9000155215, Stanford Diabetes Research Center, Diabetes Research Center (DRC), G905887895, G915808470
OpenAlex ID: W2915304695