ArticleAmerican journal of respiratory and critical care medicine2012
Longitudinal analysis casts doubt on the presence of genetic anticipation in heritable pulmonary arterial hypertension.
Article in American journal of respiratory and critical care medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 2 of them syntheses that pooled it.
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Who cites it
116 citing papers in PubMed, 2 syntheses or guidelines pooled it, 216 citations in OpenAlex.
- New progress in diagnosis and treatment of pulmonary arterial hypertension.Journal of cardiothoracic surgery · 2022Pooled it
- BMPR2 mutations and survival in pulmonary arterial hypertension: an individual participant data meta-analysis.The Lancet. Respiratory medicine · 2016Pooled it
- Trial
- A large animal model of heritable pulmonary arterial hypertension using BMPR2 gene-edited sheep.JCI insight · 2026Article
- Challenges and Strategies in Managing Pulmonary Arterial Hypertension Within the Indian Healthcare System: A Consensus Statement From the Pulmonary Vascular Research Institute India Taskforce.Pulmonary circulation · 2026Article
- A Large Animal Model of Heritable Pulmonary Arterial Hypertension Using Gene-editedbioRxiv : the preprint server for biology · 2026Article
- Risk stratification and multidisciplinary management strategies for pregnancy complicated by pulmonary arterial hypertension: a narrative review.Frontiers in endocrinology · 2026Review
- Identification of Key Genes and Pathways Associated With Gender Differences in Pulmonary Arterial Hypertension Based on Bioinformatic Approaches.BioMed research international · 2026Article
- Sex differences in pulmonary (arterial) hypertension: does it matter?Current opinion in pulmonary medicine · 2025Review
- Role of BMPR2 Mutation in Lung Organoid Differentiation.Biomedicines · 2025Article
- Bone morphogenetic protein-9 controls pulmonary vascular growth and remodeling.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- An unprecedented pathology in a 20-year-old with progressive dyspnoea and parenchymal infiltrates.Breathe (Sheffield, England) · 2025Article
- Precision Medicine for Pulmonary Vascular Disease: The Future Is Now (2023 Grover Conference Series).Pulmonary circulation · 2025Article
- Adaptation of ACMG/AMP Guidelines for Clinical Classification ofHuman mutation · 2025Article
- From basic scientific research to the development of new drugs for pulmonary arterial hypertension: insights from activin-targeting agents.Breathe (Sheffield, England) · 2025Review
- Genetics and precision genomics approaches to pulmonary hypertension.The European respiratory journal · 2024Review
- Pathology and pathobiology of pulmonary hypertension: current insights and future directions.The European respiratory journal · 2024Review
- Deep phenotyping of unaffected carriers of pathogenicThe European respiratory journal · 2024Article
- Pulmonary Hypertension Induced by Right Pulmonary Artery Occlusion: Hemodynamic Consequences ofJournal of the American Heart Association · 2024Article
- Bone morphogenetic protein signalling in pulmonary arterial hypertension: revisiting the BMPRII connection.Biochemical Society transactions · 2024Review
56 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleAnalysis of the age of onset in heritable pulmonary arterial hypertension (HPAH) has led to the hypothesis that genetic anticipation causes younger age of onset and death in subsequent generations. With accrual of pedigree data over multiple decades, we retested this hypothesis using analyses that eliminate the truncation of data that exists with shorter duration of follow-up.
objectivesTo analyze the pedigrees of families with mutations in bone morphogenetic protein receptor type 2 (BMPR2), afflicted in two or more generations with HPAH, eliminating time truncation bias by including families for whom we have at least 57 years of data.
methodsWe analyzed 355 individuals with BMPR2 mutations from 53 families in the Vanderbilt Pulmonary Hypertension Registry. We compared age at diagnosis or death in affected individuals (n = 249) by generation within families with multigenerational disease. We performed linear mixed effects models and we limited time-truncation bias by restricting date of birth to before 1955. This allowed for 57 years of follow-up (1955-2012) for mutation carriers to develop disease. We also conducted Kaplan-Meier analysis to include currently unaffected mutation carriers (n = 106). MEASUREMENTS AND MAIN
resultsDifferences in age at diagnosis by generation were found in a biased analysis that included all birth years to the present, but this finding was eliminated when the 57-year observation limit was imposed. By Kaplan-Meier analysis, inclusion of currently unaffected mutation carriers strengthens the observation that bias of ascertainment exists when recent generations are included.
conclusionsGenetic anticipation is likely an artifact of incomplete time of observation of kindreds with HPAH due to BMPR2 mutations.
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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.