Analysis of cardiac magnetic resonance imaging in 36,000 individuals yields genetic insights into dilated cardiomyopathy
Year: 2020
Type: article
Study design: Observational Study
Abstract: Dilated cardiomyopathy (DCM) is an important cause of heart failure and the leading indication for heart transplantation. Many rare genetic variants have been associated with DCM, but common variant studies of the disease have yielded few associated loci. As structural changes in the heart are a defining feature of DCM, we report a genome-wide association study of cardiac magnetic resonance imaging (MRI)-derived left ventricular measurements in 36,041 UK Biobank participants, with replication in 2184 participants from the Multi-Ethnic Study of Atherosclerosis. We identify 45 previously unreported loci associated with cardiac structure and function, many near well-established genes for Mendelian cardiomyopathies. A polygenic score of MRI-derived left ventricular end systolic volume strongly associates with incident DCM in the general population. Even among carriers of TTN truncating mutations, this polygenic score influences the size and function of the human heart. These results further implicate common genetic polymorphisms in the pathogenesis of DCM.
Source: Nature Communications
Authors: James P. Pirruccello, Alexander Bick, Minxian Wang, Mark Chaffin, Samuel Friedman, Jie Yao, Xiuqing Guo, Bharath Ambale Venkatesh, Kent D. Taylor, Wendy S. Post, Stephen Rich, Joao A. C. Lima, Jerome I. Rotter, Anthony Philippakis, Steven A. Lubitz, Patrick T. Ellinor, Amit V. Khera, Sekar Kathiresan, Krishna G. Aragam
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,380
Funders: Foundation for the National Institutes of Health, American Heart Association, Massachusetts General Hospital, Broad Institute, Fondation Leducq, National Institutes of Health, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences
Awards: G1028935811, G1052645489, G1085777395, Using genetic variation to study biology of blood lipids & coronary heart disease, G1258814100, G1261793039, G1276754516, G1286721212, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY-FIELD CENTER, G1334186997, Center for Common Disease Genetics, G1640378483, Rare variants and NHLBI traits in deeply phenotyped cohorts, Wake Forest Clinical and Translational Science Award, Precision Medicine in Ischemic Stroke and Atrial Fibrillation (PreMISe-AF), Large Scale Sequencing and Analysis of Genomes, SUBCLINICAL CARDIOVASCULAR DISEASE COORDINATING CENTER, G2078161050, G2096685756, G2144938473, G22458031, G2317004092, G232264632, G2391309017, G2436614541, G2600980409, G2623279087, G2837638605, G290884426, G291913881, G2952055171, G2952093371, G2993681707, G303055330, G3064274663, G3078883119, G3083939823, G3093995152, G3358878137, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTER, G3568487487, AFGen Consortium: Atrial Fibrillation Genomics to Functional Analyses, G3581052147, G3639969904, G3667269547, G3966146196, G3990748671, G4013255670, G4077987447, G4079570820, Genetic determinants of physical activity and association with cardiometabolic disease, G4246339746, G4401650913, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY-ULTRASOUND, G4824239441, G4831015605, G496640596, G5108002584, G5139823010, G5163278296, G5289611816, G5324596834, G556483404, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTER, G5654179670, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTER, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY, G6217957645, Advancing Atrial Fibrillation Precision Medicine, G6393075246, Institute for Clinical and Translational Research, G6541715359, G658953780, G6615318374, G66341962, G6742279884, G687975376, G6901171880, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY, G7047602405, G7109765721, G7164100729, G7249562365, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--FIELD CENTER, G7333737664, G7553146132, G7706274302, G7818715114, G78770644, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--EBCT READING, Deciphering the Genomic Topology of Atrial Fibrillation, G805458286, G8062890205, Clinical and Translational Science Award, Mentoring in Arrhythmia Research, Studies of Rare Genetic Variation in the Isolated Population of Sardinia, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY-FIELD CENTER, G8630864450, G867112777, G8754416455, G8781465314, G8852914737, G8951665900, G9000004549, G9000004784, G9000006353, G9000017360, G9000019818, G9000025517, G9000063950, G9000065698, G9000140433, Diabetes Research Center (DRC), IDENTIFICATION OF COMMON GENETIC VARIANTS FOR ATRIAL FIBRILLATION AND PR INTERVAL, UCLA Clinical and Translational Science Institute, Genomics of Cardiac Arrhythmias, G939564362, G991334795
OpenAlex ID: W3023537913