Promise and Peril of a Genotype‐First Approach to Mendelian Cardiovascular Disease
Precision medicine, which among other aspects includes an individual's genomic data in diagnosis and management, has become the standard‐of‐care for Mendelian cardiovascular disease (CVD). However, early identification and management of asymptomatic patients with potentially lethal and manageab...
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| Language: | English |
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Wiley
2024-11-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.123.033557 |
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| author | Babken Asatryan Brittney Murray Rafik Tadros Marina Rieder Ravi A. Shah Ghaith Sharaf Dabbagh Andrew P. Landstrom Stephan Dobner Patricia B. Munroe Christopher M. Haggerty Argelia Medeiros‐Domingo Anjali T. Owens Iftikhar J. Kullo Christopher Semsarian Tobias Reichlin Andreas S. Barth Dan M. Roden Cynthia A. James James S. Ware C. Anwar A. Chahal |
| author_facet | Babken Asatryan Brittney Murray Rafik Tadros Marina Rieder Ravi A. Shah Ghaith Sharaf Dabbagh Andrew P. Landstrom Stephan Dobner Patricia B. Munroe Christopher M. Haggerty Argelia Medeiros‐Domingo Anjali T. Owens Iftikhar J. Kullo Christopher Semsarian Tobias Reichlin Andreas S. Barth Dan M. Roden Cynthia A. James James S. Ware C. Anwar A. Chahal |
| author_sort | Babken Asatryan |
| collection | DOAJ |
| description | Precision medicine, which among other aspects includes an individual's genomic data in diagnosis and management, has become the standard‐of‐care for Mendelian cardiovascular disease (CVD). However, early identification and management of asymptomatic patients with potentially lethal and manageable Mendelian CVD through screening, which is the promise of precision health, remains an unsolved challenge. The reduced costs of genomic sequencing have enabled the creation of biobanks containing in‐depth genetic and health information, which have facilitated the understanding of genetic variation, penetrance, and expressivity, moving us closer to the genotype‐first screening of asymptomatic individuals for Mendelian CVD. This approach could transform health care by diagnostic refinement and facilitating prevention or therapeutic interventions. Yet, potential benefits must be weighed against the potential risks, which include evolving variant pathogenicity assertion or identification of variants with low disease penetrance; costly, stressful, and inappropriate diagnostic evaluations; negative psychological impact; disqualification for employment or of competitive sports; and denial of insurance. Furthermore, the natural history of Mendelian CVD is often unpredictable, making identification of those who will benefit from preventive measures a priority. Currently, there is insufficient evidence that population‐based genetic screening for Mendelian CVD can reduce adverse outcomes at a reasonable cost to an extent that outweighs the harms of true‐positive and false‐positive results. Besides technical, clinical, and financial burdens, ethical and legal aspects pose unprecedented challenges. This review highlights key developments in the field of genotype‐first approaches to Mendelian CVD and summarizes challenges with potential solutions that can pave the way for implementing this approach for clinical care. |
| format | Article |
| id | doaj-art-ff5b6bf384334df490087617c1fe6fde |
| institution | OA Journals |
| issn | 2047-9980 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-ff5b6bf384334df490087617c1fe6fde2025-08-20T01:54:22ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-11-01132110.1161/JAHA.123.033557Promise and Peril of a Genotype‐First Approach to Mendelian Cardiovascular DiseaseBabken Asatryan0Brittney Murray1Rafik Tadros2Marina Rieder3Ravi A. Shah4Ghaith Sharaf Dabbagh5Andrew P. Landstrom6Stephan Dobner7Patricia B. Munroe8Christopher M. Haggerty9Argelia Medeiros‐Domingo10Anjali T. Owens11Iftikhar J. Kullo12Christopher Semsarian13Tobias Reichlin14Andreas S. Barth15Dan M. Roden16Cynthia A. James17James S. Ware18C. Anwar A. Chahal19Division of Cardiology, Department of Medicine Johns Hopkins University School of Medicine Baltimore MD USADivision of Cardiology, Department of Medicine Johns Hopkins University School of Medicine Baltimore MD USACardiovascular Genetics Centre Montréal Heart Institute Montréal Québec CanadaDepartment of Cardiology Inselspital, Bern University Hospital, University of Bern Bern SwitzerlandRoyal Brompton Hospital, Guy’s and St Thomas’ NHS Foundation Trust London United KingdomCenter for Inherited Cardiovascular Diseases WellSpan Health Lancaster PA USADivision of Cardiology, Department of Pediatrics, and Department of Cell Biology Duke University School of Medicine Durham NC USADepartment of Cardiology Inselspital, Bern University Hospital, University of Bern Bern SwitzerlandNIHR Barts Biomedical Research Centre William Harvey Research Institute, Queen Mary University of London London United KingdomDepartment of Translational Data Science and Informatics Heart Institute, Geisinger Danville PA USASwiss DNAlysis Dübendorf SwitzerlandCenter for Inherited Cardiovascular Disease, Cardiovascular Division University of Pennsylvania Perelman School of Medicine Philadelphia PA USADepartment of Cardiovascular Medicine Mayo Clinic Rochester MN USAAgnes Ginges Centre for Molecular Cardiology at Centenary Institute, The University of Sydney Sydney New South Wales AustraliaDepartment of Cardiology Inselspital, Bern University Hospital, University of Bern Bern SwitzerlandDivision of Cardiology, Department of Medicine Johns Hopkins University School of Medicine Baltimore MD USADepartment of Medicine, Pharmacology, and Biomedical Informatics Vanderbilt University Medical Center Nashville TN USADivision of Cardiology, Department of Medicine Johns Hopkins University School of Medicine Baltimore MD USAProgram in Medical and Population Genetics Broad Institute of MIT and Harvard Cambridge MA USACenter for Inherited Cardiovascular Diseases WellSpan Health Lancaster PA USAPrecision medicine, which among other aspects includes an individual's genomic data in diagnosis and management, has become the standard‐of‐care for Mendelian cardiovascular disease (CVD). However, early identification and management of asymptomatic patients with potentially lethal and manageable Mendelian CVD through screening, which is the promise of precision health, remains an unsolved challenge. The reduced costs of genomic sequencing have enabled the creation of biobanks containing in‐depth genetic and health information, which have facilitated the understanding of genetic variation, penetrance, and expressivity, moving us closer to the genotype‐first screening of asymptomatic individuals for Mendelian CVD. This approach could transform health care by diagnostic refinement and facilitating prevention or therapeutic interventions. Yet, potential benefits must be weighed against the potential risks, which include evolving variant pathogenicity assertion or identification of variants with low disease penetrance; costly, stressful, and inappropriate diagnostic evaluations; negative psychological impact; disqualification for employment or of competitive sports; and denial of insurance. Furthermore, the natural history of Mendelian CVD is often unpredictable, making identification of those who will benefit from preventive measures a priority. Currently, there is insufficient evidence that population‐based genetic screening for Mendelian CVD can reduce adverse outcomes at a reasonable cost to an extent that outweighs the harms of true‐positive and false‐positive results. Besides technical, clinical, and financial burdens, ethical and legal aspects pose unprecedented challenges. This review highlights key developments in the field of genotype‐first approaches to Mendelian CVD and summarizes challenges with potential solutions that can pave the way for implementing this approach for clinical care.https://www.ahajournals.org/doi/10.1161/JAHA.123.033557biobankcardiac arrhythmiacardiomyopathygeneticsprecision healthprecision medicine sudden cardiac death |
| spellingShingle | Babken Asatryan Brittney Murray Rafik Tadros Marina Rieder Ravi A. Shah Ghaith Sharaf Dabbagh Andrew P. Landstrom Stephan Dobner Patricia B. Munroe Christopher M. Haggerty Argelia Medeiros‐Domingo Anjali T. Owens Iftikhar J. Kullo Christopher Semsarian Tobias Reichlin Andreas S. Barth Dan M. Roden Cynthia A. James James S. Ware C. Anwar A. Chahal Promise and Peril of a Genotype‐First Approach to Mendelian Cardiovascular Disease Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease biobank cardiac arrhythmia cardiomyopathy genetics precision health precision medicine sudden cardiac death |
| title | Promise and Peril of a Genotype‐First Approach to Mendelian Cardiovascular Disease |
| title_full | Promise and Peril of a Genotype‐First Approach to Mendelian Cardiovascular Disease |
| title_fullStr | Promise and Peril of a Genotype‐First Approach to Mendelian Cardiovascular Disease |
| title_full_unstemmed | Promise and Peril of a Genotype‐First Approach to Mendelian Cardiovascular Disease |
| title_short | Promise and Peril of a Genotype‐First Approach to Mendelian Cardiovascular Disease |
| title_sort | promise and peril of a genotype first approach to mendelian cardiovascular disease |
| topic | biobank cardiac arrhythmia cardiomyopathy genetics precision health precision medicine sudden cardiac death |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.123.033557 |
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