A5043668018- Cardiomyopathy and Myosin Studies
- Cardiac electrophysiology and arrhythmias
- Genetic Associations and Epidemiology
- Genomics and Rare Diseases
- Cardiac Arrhythmias and Treatments
- Atrial Fibrillation Management and Outcomes
- ECG Monitoring and Analysis
- Lipoproteins and Cardiovascular Health
- Ion channel regulation and function
- Congenital heart defects research
- Cancer-related gene regulation
- Cardiovascular Function and Risk Factors
- Viral Infections and Immunology Research
- RNA Research and Splicing
- Cardiovascular Disease and Adiposity
- Health Systems, Economic Evaluations, Quality of Life
- Cardiovascular Effects of Exercise
- Thyroid Disorders and Treatments
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Phonocardiography and Auscultation Techniques
- Cardiovascular Syncope and Autonomic Disorders
- Genomic variations and chromosomal abnormalities
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Genetic Neurodegenerative Diseases
- Electrostatic Discharge in Electronics
University of Copenhagen
2016-2025
Rigshospitalet
2016-2025
Copenhagen University Hospital
2015-2024
Royal Gustavus Adolphus Academy
2021
Danish National Research Foundation
2015-2019
Abstract We report a multi-ancestry genome-wide association study on liver cirrhosis and its associated endophenotypes, alanine aminotransferase (ALT) γ-glutamyl transferase. Using data from 12 cohorts, including 18,265 cases with cirrhosis, 1,782,047 controls, up to 1 million individuals function tests validation cohort of 21,689 617,729 we identify validate 14 risk associations for cirrhosis. Many variants are located near genes involved in hepatic lipid metabolism. One these, PNPLA3...
A family history of atrial fibrillation constitutes a substantial risk developing the disease, however, pathogenesis this complex disease is poorly understood. We perform whole-exome sequencing on 24 families with at least three members diagnosed (AF) and find that titin-truncating variants (TTNtv) are significantly enriched in these patients (P = 1.76 × 10-6). This finding replicated an independent cohort early-onset lone AF (n 399; odds ratio 36.8; P 4.13 CRISPR/Cas9 modified zebrafish...
Abstract Recent global developments underscore the prominent role big data have in modern medical science. But privacy issues constitute a prevalent problem for collecting and sharing between researchers. However, synthetic generated to represent real carrying similar information distribution may alleviate issue. In this study, we present generative adversarial networks (GANs) capable of generating realistic DeepFake 10-s 12-lead electrocardiograms (ECGs). We developed compared two methods,...
Abstract Aims Atrial fibrillation (AF) is the most common type of cardiac arrhythmias, whose incidence likely to increase with aging population. It considered a progressive condition, frequently observed as complication other cardiovascular disorders. However, recent genetic studies revealed presence several mutations and variants linked AF, findings that define AF multifactorial disease. Due complex genetics paucity models, molecular mechanisms underlying initiation are still poorly...
Abstract Deep learning-based tools may annotate and interpret medical data more quickly, consistently, accurately than doctors. However, as doctors are ultimately responsible for clinical decision-making, any deep prediction should be accompanied by an explanation that a human can understand. We present approach called electrocardiogram gradient class activation map (ECGradCAM), which is used to generate attention maps explain the reasoning behind decision-making in ECG analysis. Attention...
Abstract Aims Left atrial (LA) volume and function impose significant impact on cardiovascular pathogenesis if compromised. We aimed at investigating the genetic architecture of LA using cardiac magnetic resonance imaging data. Methods results used UK Biobank, which is a large prospective population study with available phenotypic On subset 35 658 European individuals, we performed genome-wide association studies five volumetric functional variables, generated machine learning algorithm. In...
Abstract The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration JT interval, respectively. abnormalities are associated with potentially fatal arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 121 independent loci for QT, QRS, respectively, including a male-specific X-chromosome locus. gene-based rare-variant methods, associations Mendelian disease...
AimsWe studied whether variants previously associated with congenital long QT syndrome (cLQTS) have an effect on the QTc interval in a Danish population sample. Furthermore, we assessed carriers of cLQTS-associated genes are more prone to experience syncope compared non-carriers and increased mortality non-carriers.
We showed an association between atrial fibrillation and rare loss-of-function (LOF) variants in the cardiac splicing regulator RBM20 2 independent cohorts. In a rat model with loss of RBM20, we demonstrated altered sarcomere genes (NEXN, TTN, TPM1, MYOM1, LDB3), differential expression key genes. identified mitochondrial structure on electron microscopy imaging found compromised function. Finally, that 3 novel LOF patients fibrillation, lead to significantly reduced activity. Our results...
Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. The major AF susceptibility locus 4q25 establishes long-range interactions with promoter PITX2, a transcription factor gene critical functions during development. While many AF-linked loci have been identified in genome-wide association studies, mechanistic understanding into how genetic variants, including those at locus, increase vulnerability to mostly lacking. Here, we show that loss pitx2c zebrafish leads adult...
Abstract Background and Aims Familial ST-depression syndrome (FSTD) is a recently identified inherited cardiac disease associated with arrhythmias systolic dysfunction. The underlying genetic aetiology has remained elusive. This study aimed at finding the causative variant. Methods A total of 67 FSTD patients (20 families) were studied. Linkage analysis whole-genome sequencing (WGS) initially performed. An non-coding variant was functionally characterized in AC16 human cardiomyocytes, muscle...
Catecholaminergic Polymorphic Ventricular Tachycardia ( CPVT ) is a highly lethal cardiac arrhythmia disease occurring during exercise or psychological stress. has an estimated prevalence of 1:10,000 and mainly been associated with variants in calcium‐regulating genes. Identification potential false‐positive pathogenic was conducted by searching the Exome Aggregation Consortium ExAC database n = 60,706) for reported to be . The pathogenicity interrogated assessed using guidelines from...
Background Hundreds of genetic variants have been described as disease causing in dilated cardiomyopathy (DCM). Some these associations are now being questioned. We aimed to identify the prevalence previously DCM associated Exome Aggregation Consortium (ExAC), order potentially false-positive variants. Methods Variants listed disease-causing Human Gene Mutation Database were extracted from ExAC. Pathogenicity predictions for mined dbNSFP v 2.9 database. Results Of 473 HGMD, 148 (31%) found...
Abstract Atrial fibrillation (AF) has traditionally been considered an electrical heart disease. However, genetic studies have revealed that the structural architecture of also play a significant role. We evaluated functional and consequences harboring titin-truncating variant (TTNtv) in AF patients, using cardiac magnetic resonance (CMR). Seventeen early-onset cases carrying TTNtv, were matched 1:1 with non-AF controls replication cohort without underwent CMR. Cardiac volumes left atrial...
To search for sequence variants associated with ACEi discontinuation and to test their association ACEi-associated adverse drug reactions (ADRs).
Abstract Aims Syncope is a common condition associated with frequent hospitalization or visits to the emergency department. Family aggregation and twin studies have shown that syncope has heritable component. We investigated whether genetic variants predispose collapse. Methods results used genome-wide association data on 408 961 individuals European ancestry from UK Biobank study. In replication study, we Integrative Psychiatric Research Consortium (iPSYCH) cohort (n = 86 189), investigate...
Atrial fibrillation (AF) is the most common cardiac arrhythmia, and it associated with an increased risk of heart failure, stroke, dementia, death. Recently, titin-truncating variants (TTNtv), which are predominantly dilated cardiomyopathy (DCM), were early-onset AF. Furthermore, genome-wide association studies (GWAS) AF other structural genes. In this study, we investigated whether was loss-of-function in DCM-associated genes encoding cytoskeletal proteins. Using targeted sequencing,...
Abstract Atrial Fibrillation (AF) is the most common cardiac arrhythmia. Its pathogenesis complex and poorly understood. Whole exome sequencing of Danish families with AF revealed a novel four nucleotide deletion c.1041_1044del in CLCN2 shared by affected individuals. We aimed to investigate role genetic variation encoding inwardly rectifying chloride channel ClC-2 as risk factor for development familiar AF. The effect variant was evaluated electrophysiological recordings on transiently...