Year: 2018
Type: article
Study design: Observational Study
Abstract: Aims: Sudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. We aim to identify potential loci associated with SCA and to identify risk factors causally associated with SCA. Methods and results: We carried out a large genome-wide association study (GWAS) for SCA (n = 3939 cases, 25 989 non-cases) to examine common variation genome-wide and in candidate arrhythmia genes. We also exploited Mendelian randomization (MR) methods using cross-trait multi-variant genetic risk score associations (GRSA) to assess causal relationships of 18 risk factors with SCA. No variants were associated with SCA at genome-wide significance, nor were common variants in candidate arrhythmia genes associated with SCA at nominal significance. Using cross-trait GRSA, we established genetic correlation between SCA and (i) coronary artery disease (CAD) and traditional CAD risk factors (blood pressure, lipids, and diabetes), (ii) height and BMI, and (iii) electrical instability traits (QT and atrial fibrillation), suggesting aetiologic roles for these traits in SCA risk. Conclusions: Our findings show that a comprehensive approach to the genetic architecture of SCA can shed light on the determinants of a complex life-threatening condition with multiple influencing factors in the general population. The results of this genetic analysis, both positive and negative findings, have implications for evaluating the genetic architecture of patients with a family history of SCA, and for efforts to prevent SCA in high-risk populations and the general community.
Source: European Heart Journal
Authors: Foram N. Ashar, Rebecca N. Mitchell, Christine M. Albert, Christopher Newton-Cheh, Jennifer A. Brody, Martina Muller-Nurasyid, Anna Moes, Thomas Meitinger, Angel Mak, Heikki Huikuri, M. Juhani Junttila, Philippe Goyette, Sara L. Pulit, Raha Pazoki, Michael W. Tanck, Marieke T. Blom, XiaoQing Zhao, Aki S. Hauvlinna, Reza Jabbari, Charlotte Glinge, Vinicius Tragante, Stefan A. Escher, Aravinda Chakravarti, Georg Ehret, Josef Coresh, Man Li, Ronald J. Prineas, Oscar H. Franco, Pui-Yan Kwok, Thomas Lumley, Florence Dumas, Barbara McKnight, Jerome I. Rotter, Rozenn N. Lemaitre, Susan R. Heckbert, Christopher J. O’Donnell, Shih-Jen Hwang, Jean-Claude Tardif, Marja-Leena Kortelainen, Martin VanDenburgh, Andre G. Uitterlinden, Albert Hofman, Bruno H.C. Stricker, Paul I.W. de Bakker, Paul W. Franks, Jan-Hakan Jansson, Folkert W. Asselbergs, Marc K. Halushka, Joseph J. Maleszewski, Jacob Tfelt-Hansen, Thomas Engstrom, Veikko Salomaa, Renu Virmani, Frank Kolodgie, Arthur A.M. Wilde, Hanno L. Tan, Connie R. Bezzina, Mark Eijgelsheim, John D. Rioux, Xavier Jouven, Stefan Kaab, Bruce M. Psaty, David S. Siscovick, Dan Arking, Nona Sotoodehnia
Institutions: Johns Hopkins University, Brigham and Women's Hospital, Massachusetts General Hospital, University of Washington, German Centre for Cardiovascular Research, Ludwig-Maximilians-Universität München, TUM Klinikum, Helmholtz Munich, Institut für Humangenetik, Technical University of Munich, University of California, San Francisco, Oulu University Hospital, University of Oulu, Montreal Heart Institute, Université de Montréal, Utrecht University, University Medical Center Utrecht, St Mary's Hospital, Imperial College London, Amsterdam UMC Location University of Amsterdam, CVPath Institute, Finnish Institute for Health and Welfare, Rigshospitalet, Lund University, Skåne University Hospital, Wake Forest University Health Sciences, Wake Forest University, University of Bern, Erasmus MC, University of Auckland, Inserm, Sorbonne Paris Cité, Paris Cardiovascular Research Center, The Lundquist Institute, Harbor–UCLA Medical Center, VA Boston Healthcare System, Framingham Heart Study, University Hospital of Umeå, Skellefteå Hospital, Umeå University, University College London, Johns Hopkins Medicine, Mayo Clinic, University of Copenhagen, Amsterdam University Medical Centers, Amsterdam Cardiovascular Sciences, University of Amsterdam, University Medical Center Groningen, New York Academy of Medicine
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: U.S. Department of Agriculture, School of Medicine, Boston University, Foundation for Cardiovascular Research, University of Washington, Johns Hopkins University, US-UK Fulbright Commission, European Commission, National Research Foundation, Agence Nationale de la Recherche, Fondation Leducq, Institut National de la Santé et de la Recherche Médicale, Danmarks Grundforskningsfond, ZonMw, Ministry of Earth Sciences, Academy of Finland, Bundesministerium für Bildung und Forschung, College ter Beoordeling van Geneesmiddelen, Erasmus Medisch Centrum, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Lunds Universitet, Universitair Medisch Centrum Groningen, Rigshospitalet, Sydäntutkimussäätiö, Center for Translational Molecular Medicine, Oulun Yliopisto, Novo Nordisk Fonden, Fondation Institut de Cardiologie de Montréal, Institut de Cardiologie de Montréal, National Institutes of Health, Department of Pathology, Johns Hopkins University, Helmholtz Zentrum München, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Neurological Disorders and Stroke, National Center for Research Resources, National Center for Advancing Translational Sciences, Sociale en Geesteswetenschappen, NWO
Awards: G1011819373, G1023702118, G1028935811, G1052397333, G1135917780, G1168185457, G1214533002, G1220223050, G1224608327, G1243299691, G125972088, CORONARY HEART DISEASE AND STROKE, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G1318872084, G1327305488, G1329491795, G1332411685, G1337262289, G1436665097, G1460387277, G1481755545, G1495020029, G1527150935, G15705064, CORONARY HEART DISEASE AND STROKE, G1691174148, G173303992, G1929859193, G1941623656, G195474297, Genome-wide case-only study of antihypertensive drug-gene interactions, G2111759553, G2145550945, G2167231433, Rare variants and NHLBI traits in deeply phenotyped cohorts, G2188752979, G2194386449, G2198974105, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G232264632, G2334180555, Genomics of Cardiac Electrical Activity and Arrhythmia, G2391884931, G241213959, G247538147, G250621538, Exceptional Survival: Trajectories to Functional Aging (CHS All Stars), G2541934785, GENOMICS OF SUDDEN CARDIAC ARREST, CORONARY HEART DISEASE &STROKE IN THE ELDERLY, G270907595, G2750880407, G276595759, European Sudden Cardiac Arrest network: towards Prevention, Education and NEw Treatment, G2800149121, G2818629771, G2818913090, G2859083839, G297113894, G300339986, G301743239, G3045517347, WGA Study to Identify Genetic Variants Associated with CV Events in CHS, G3114902838, G313509969, G3152385821, Prospective meta-analyses of drug-gene interactions: CHARGE GWAS consortium, G3220743633, G3237031833, G3256118428, G3283060913, G3410686264, G3426488059, G3428241583, G34347772, G343705321, G3462919067, CHS research resources for the cardiovascular health of older adults, G3540777072, G3568570436, Dietary Etiologies of Heart Disease, G3692229207, G36937976, G3839646794, G3852491038, Dietary and Hormonal Determinants of Cancer in Women, CENTRAL BLOOD ANALYSIS LABORATORY FOR CHS, Genomics of Sudden Cardiac Arrest Among African Americans, G4167445418, G4200864717, G4225032190, G423252844, G434337789, G438589988, G4429312988, G445457422, G4461738597, Pre-DETERMINE: Biologic Markers and MRI SCD Cohort Study, G4522543292, G457330776, G4582778782, G4680910104, G4769319072, G4824283243, G4862466940, G494123624, G5031471085, G5074086979, G5086681883, G5125936451, G5164707915, G5251985303, G536099884, Genome-Wide Association for Loci Influencing CHD and Other Heart, Lung and Blood, Physicians' Health Study II: Prevention Trial of Vitamins, G5457026379, G5479317095, G5503814514, Epidemiology of Venous Thrombosis and Pulmonary Embolism, G565003982, G567847597, G5684079324, G5709329001, G573134505, G581887176, G587458537, CHS Events Follow-up Study, G6008908520, G609820727, G6195637971, G6226795708, The Framingham Heart Study, TRIAL OF ASPIRIN AND BETA-CAROTENE IN U S MD'S, G6548750934, G6552090923, G6592708301, G6790886393, G6834727893, G6902273418, Functional Dissection of the Sudden Cardiac Death Associated BAZ2B locus, G716312657, G7169564462, G7176672723, Prospective Studies of Diet and Cancer in Men and Women, G772621625, G7821931760, G80149192, G8260701975, G8506930532, G8554986239, CHS-Transition Phase -268055222, G890705022, G8927421343, G8937114048, G9000018826, G9000022020, G9000026278, G9000027259, G9000031392, G9000035944, G9000046001, G9000069684, G9000069887, G9000106048, G9000124008, G9000124674, G9000133315, G9000139054, G9000140433, G9000155215, G9000190097, Diabetes Research Center (DRC), From GWAS loci to blood pressure genes, variants & mechanisms - Renewal, RISK FACTORS FOR CVD IN WOMEN, G905887895, G931818222, G939971039, G973459597, G984894956
OpenAlex ID: W2777050540