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The Capital Region of Denmark - a part of Copenhagen University Hospital
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Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

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  1. Combined burden and functional impact tests for cancer driver discovery using DriverPower

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  2. Genomic footprints of activated telomere maintenance mechanisms in cancer

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  3. Pathway and network analysis of more than 2500 whole cancer genomes

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  4. Prenatal dietary supplements influence the infant airway microbiota in a randomized factorial clinical trial

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  1. Potassium Disturbances and Risk of Ventricular Fibrillation Among Patients With ST-Segment-Elevation Myocardial Infarction

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  2. Regional variation in out-of-hospital cardiac arrest: incidence and survival - a nationwide study of regions in Denmark

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  3. Time in therapeutic range and risk of thromboembolism and bleeding in patients with a mechanical heart valve prosthesis

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  4. Coffee intake protects against symptomatic gallstone disease in the general population: a Mendelian randomization study

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  • Regeneron Genetics Center
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Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.

Original languageEnglish
JournalNature Communications
Volume11
Issue number1
Pages (from-to)163
ISSN2041-1723
DOIs
Publication statusPublished - 9 Jan 2020

ID: 58961530