ArticleCirculation2019
Genomics-First Evaluation of Heart Disease Associated With Titin-Truncating Variants.
Article in Circulation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 85 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
85 citing papers in PubMed, 155 citations in OpenAlex.
- Effects of SGLT2 inhibition on incident heart failure in carriers of cardiomyopathy-associated genetic variants.Nature medicine · 2026Trial
- When Virchow's Triad Goes on Overdrive: Catastrophic Multi-System Thrombosis in the Setting of New-Onset Heart Failure in a Previously Healthy Man.Journal of medical cases · 2026Article
- Association of Common Ancestry-Enriched Variants With Cardiomyopathy and Arrhythmias.Circulation · 2026Article
- Epidemiology of non-ischaemic dilated cardiomyopathy.Nature reviews. Cardiology · 2026Review
- RNA-Based Therapies for Treating Monogenic Cardiomyopathies.The Canadian journal of cardiology · 2026Review
- Truncating Variants inJournal of the American Heart Association · 2026Article
- Mending the Achilles heels of titin in cardiac and musculoskeletal disease.Biophysical reviews · 2026Review
- Leveraging Single-Cell Technologies to Advance Understanding of Myocardial Disease.Circulation research · 2026Review
- TTN variants in pediatric cardiomyopathy: a retrospective cohort study.Frontiers in genetics · 2026Article
- Titin-related familial dilated cardiomyopathy: factors associated with disease onset.European heart journal · 2025Observational
- Spectrum and Clinical Interpretation ofInternational journal of molecular sciences · 2025Article
- The Utility of Genome-Wide Association Studies in Inherited Arrhythmias and Cardiomyopathies.Genes · 2025Review
- Prevalence of deleterious variants in cardiomyopathy genes in early-onset atrial fibrillation.Research square · 2025Article
- An African ancestry-specific nonsense variant in CD36 is associated with a higher risk of dilated cardiomyopathy.Nature genetics · 2025Article
- Age-Dependent Contributions of Rare and Common Genetic Variation in Atrial Fibrillation.Circulation. Genomic and precision medicine · 2025Article
- Mechanically knocking out titin reveals protein tension loss as a trigger of muscle disease.Nature biomedical engineering · 2025Article
- Research Progress on the Association Between GLP-1 Receptor Agonists and Cardiomyopathy.Reviews in cardiovascular medicine · 2025Review
- Formation of an Amyloid-like Structure During In Vitro Interaction of Titin and Myosin-Binding Protein C.International journal of molecular sciences · 2025Article
- Titin-Truncating variants predispose to dilated cardiomyopathy in populations genetically similar to african and european reference populations.PLoS genetics · 2025Article
- Environmental Risk Factors Are Associated With the Natural History of Familial Dilated Cardiomyopathy.Journal of the American Heart Association · 2025Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
39 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundTruncating variants in the Titin gene (TTNtvs) are common in individuals with idiopathic dilated cardiomyopathy (DCM). However, a comprehensive genomics-first evaluation of the impact of TTNtvs in different clinical contexts, and the evaluation of modifiers such as genetic ancestry, has not been performed.
methodsWe reviewed whole exome sequence data for >71 000 individuals (61 040 from the Geisinger MyCode Community Health Initiative (2007 to present) and 10 273 from the PennMedicine BioBank (2013 to present) to identify anyone with TTNtvs. We further selected individuals with TTNtvs in exons highly expressed in the heart (proportion spliced in [PSI] >0.9). Using linked electronic health records, we evaluated associations of TTNtvs with diagnoses and quantitative echocardiographic measures, including subanalyses for individuals with and without DCM diagnoses. We also reviewed data from the Jackson Heart Study to validate specific analyses for individuals of African ancestry.
resultsIdentified with a TTNtv in a highly expressed exon (hiPSI) were 1.2% individuals in PennMedicine BioBank and 0.6% at Geisinger. The presence of a hiPSI TTNtv was associated with increased odds of DCM in individuals of European ancestry (odds ratio [95% CI]: 18.7 [9.1-39.4] {PennMedicine BioBank} and 10.8 [7.0-16.0] {Geisinger}). hiPSI TTNtvs were not associated with DCM in individuals of African ancestry, despite a high DCM prevalence (odds ratio, 1.8 [0.2-13.7]; P=0.57). Among 244 individuals of European ancestry with DCM in PennMedicine BioBank, hiPSI TTNtv carriers had lower left ventricular ejection fraction (β=-12%, P=3×10
conclusionsIndividuals of European ancestry with hiPSI TTNtv have an abnormal cardiac phenotype characterized by lower left ventricular ejection fraction, irrespective of the clinical manifestation of cardiomyopathy. Associations with arrhythmias, including atrial fibrillation, were observed even when controlling for cardiomyopathy diagnosis. In contrast, no association between hiPSI TTNtvs and DCM was discerned among individuals of African ancestry. Given these findings, clinical identification of hiPSI TTNtv carriers may alter clinical management strategies.
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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 OpenQuestion graph.