ArticleEuropean heart journal2021
Genetic insight into sick sinus syndrome.
Article in European heart journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 3 of them syntheses that pooled it.
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Who cites it
29 citing papers in PubMed, 3 syntheses or guidelines pooled it, 61 citations in OpenAlex.
- Genetic insights into cardiac conduction disorders from genome-wide association studies.Human genomics · 2025Pooled it
- Sex hormones and reproductive factors with cardiac arrhythmia and ECG indices: a mendelian randomization study.BMC cardiovascular disorders · 2024Pooled it
- Predictors of pacemaker requirement in patients with implantable loop recorder and unexplained syncope: A systematic review and meta-analysis.Clinical cardiology · 2024Pooled it
- Beyond mean heart dose: differentiated electrocardiographic manifestations and dosimetric mechanisms of cardiac injury in left-sided versus right-sided breast cancer after intensity-modulated radiotherapy.Frontiers in oncology · 2026Article
- Electromechanical and structural phenotypes from cardiac imaging and epicardial mapping in inherited arrhythmia syndromes.Frontiers in cardiovascular medicine · 2026Review
- PITX2 dosage-dependent changes in pacemaker cell state underlie sinus node dysfunction and atrial arrhythmias.Nature communications · 2025Article
- Epistasis regulates genetic control of cardiac hypertrophy.Nature cardiovascular research · 2025Article
- Deciphering epistatic genetic regulation of cardiac hypertrophy.medRxiv : the preprint server for health sciences · 2025Article
- Causality of Childhood and Adult Body Mass Index on Sick Sinus Syndrome: A Mendelian Randomization Study.Cureus · 2025Article
- A pathogenic titin missense mutation in hiPSC-derived cardiomyocytes predisposes to ventricular fibrillation in acute ST-segment elevation myocardial infarction.Frontiers in cardiovascular medicine · 2025Article
- Causal Effect of Obstructive Sleep Apnea on Sick Sinus Syndrome: A Bidirectional Mendelian Randomization Study.Nature and science of sleep · 2025Article
- The impact of common and rare genetic variants on bradyarrhythmia development.Nature genetics · 2025Article
- Familial risk of sinus node dysfunction indicating pacemaker implantation: a nationwide cohort study.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2024Article
- Increased pacemaker implantation and mortality rates in relatives of patients with early-onset sinus node dysfunction: can genetics explain all?Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2024Article
- Fine mapping of candidate effector genes for heart rate.Human genetics · 2024Article
- Mitochondrial dysfunction is a key link involved in the pathogenesis of sick sinus syndrome: a review.Frontiers in cardiovascular medicine · 2024Review
- Article
- Epistasis regulates genetic control of cardiac hypertrophy.Research square · 2023Article
- Pulmonary Hypertension Is Associated with Worse Outcomes in Patients Hospitalized for Sick Sinus Syndrome.The Journal of innovations in cardiac rhythm management · 2023Article
- Clinical Predictors of Pacing Device Implantation in Implantable Cardiac Monitor Recipients for Unexplained Syncope.CJC open · 2023Article
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Authors and funding
45 authors at 13 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThe aim of this study was to use human genetics to investigate the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors in its development. METHODS AND
resultsWe performed a genome-wide association study of 6469 SSS cases and 1 000 187 controls from deCODE genetics, the Copenhagen Hospital Biobank, UK Biobank, and the HUNT study. Variants at six loci associated with SSS, a reported missense variant in MYH6, known atrial fibrillation (AF)/electrocardiogram variants at PITX2, ZFHX3, TTN/CCDC141, and SCN10A and a low-frequency (MAF = 1.1-1.8%) missense variant, p.Gly62Cys in KRT8 encoding the intermediate filament protein keratin 8. A full genotypic model best described the p.Gly62Cys association (P = 1.6 × 10-20), with an odds ratio (OR) of 1.44 for heterozygotes and a disproportionally large OR of 13.99 for homozygotes. All the SSS variants increased the risk of pacemaker implantation. Their association with AF varied and p.Gly62Cys was the only variant not associating with any other arrhythmia or cardiovascular disease. We tested 17 exposure phenotypes in polygenic score (PGS) and Mendelian randomization analyses. Only two associated with the risk of SSS in Mendelian randomization, AF, and lower heart rate, suggesting causality. Powerful PGS analyses provided convincing evidence against causal associations for body mass index, cholesterol, triglycerides, and type 2 diabetes (P > 0.05).
conclusionWe report the associations of variants at six loci with SSS, including a missense variant in KRT8 that confers high risk in homozygotes and points to a mechanism specific to SSS development. Mendelian randomization supports a causal role for AF in the development of SSS.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.