ReviewCirculation2019
Beyond the One Gene-One Disease Paradigm: Complex Genetics and Pleiotropy in Inheritable Cardiac Disorders
Review in Circulation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
80 citing papers in PubMed, 1 synthesis or guideline pooled it, 135 citations in OpenAlex.
- Pooled it
- International Evidence Based Reappraisal of Genes Associated With Arrhythmogenic Right Ventricular Cardiomyopathy Using the Clinical Genome Resource Framework.Circulation. Genomic and precision medicine · 2021Trial
- Automated patch clamp data improve variant classification and penetrance stratification for SCN5A-Brugada syndrome.European heart journal · 2026Article
- Yield of Family Screening in Arrhythmogenic Right Ventricular Cardiomyopathy Without a Validated Genetic Cause.Circulation. Arrhythmia and electrophysiology · 2026Article
- Phenotypic manifestation of Brugada syndrome after living donor liver transplantation accompanied by normalization of sex hormone levels.HeartRhythm case reports · 2026Article
- Epigenetics, Modifiers, and Molecular Noise: Rethinking Pathophysiology in Dilated and Hypertrophic Cardiomyopathies.International journal of molecular sciences · 2026Review
- Genome-Wide Association Studies of Myocardial Infarction: A Systematic Literature Review.Journal of cardiovascular development and disease · 2026Review
- Molecular genotype-phenotype correlation in ACTB- and ACTG1-related non-muscle actinopathies.American journal of human genetics · 2026Article
- Genetics of supraventricular tachycardia: current evidence with a focus on translational relevance and personalized medicine.Frontiers in cardiovascular medicine · 2026Review
- Genetic and Genomic Testing in Cardiovascular Disease: A Policy Statement From the American Heart Association.Circulation · 2025Review
- The Utility of Genome-Wide Association Studies in Inherited Arrhythmias and Cardiomyopathies.Genes · 2025Review
- A combined genomic arrhythmia propensity score delineates cumulative risk.Cell reports. Medicine · 2025Article
- Benchmark of computational methods to detect digenism in sequencing data.European journal of human genetics : EJHG · 2025Review
- Making Sense of Missense: Benchmarking MutScore for Variant Interpretation in Inherited Cardiac Diseases.Molecular diagnosis & therapy · 2025Article
- Nomogram for prediction of in-hospital mortality rate in children with congenital heart disease in pediatric intensive care: establishment and external validation.Translational pediatrics · 2025Article
- Oligogenic effect is associated with the clinical heterogeneity of autosomal dominant deafness-15.Scientific reports · 2025Article
- Genetics of Sudden Cardiac Arrest: Overview of Genetic Risk Factors and Aetiologies.Arrhythmia & electrophysiology review · 2025Review
- Promise and Peril of a Genotype-First Approach to Mendelian Cardiovascular Disease.Journal of the American Heart Association · 2024Review
- FLT4 causes developmental disorders of the cardiovascular and lymphovascular systems via pleiotropic molecular mechanisms.Cardiovascular research · 2024Article
- Major Causes of Conflicting Interpretations of Variant Pathogenicity in Rare Disease: A Systematic Analysis.Journal of personalized medicine · 2024Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Inheritable cardiac disorders, which may be associated with cardiomyopathic changes, are often associated with increased risk of sudden death in the young. Early linkage analysis studies in Mendelian forms of these diseases, such as hypertrophic cardiomyopathy and long-QT syndrome, uncovered large-effect genetic variants that contribute to the phenotype. In more recent years, through genotype-phenotype studies and methodological advances in genetics, it has become evident that most inheritable cardiac disorders are not monogenic but, rather, have a complex genetic basis wherein multiple genetic variants contribute (oligogenic or polygenic inheritance). Conversely, studies on genes underlying these disorders uncovered pleiotropic effects, with a single gene affecting multiple and apparently unrelated phenotypes. In this review, we explore these 2 phenomena: on the one hand, the evidence that variants in multiple genes converge to generate one clinical phenotype, and, on the other, the evidence that variants in one gene can lead to apparently unrelated phenotypes. Although multiple conditions are addressed to illustrate these concepts, the experience obtained in the study of long-QT syndrome, Brugada syndrome, and arrhythmogenic cardiomyopathy, and in the study of functions related to SCN5A (the gene coding for the α-subunit of the most abundant sodium channel in the heart) and PKP2 (the gene coding for the desmosomal protein plakophilin-2), as well, is discussed in more detail.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.