| Title: |
Promise and Peril of a Genotype-First Approach to Mendelian Cardiovascular Disease. |
| Authors: |
Asatryan, B; Murray, B; Tadros, R; Rieder, M; Shah, RA; Sharaf Dabbagh, G; Landstrom, AP; Dobner, S; Munroe, PB; Haggerty, CM; Medeiros-Domingo, A; Owens, AT; Kullo, IJ; Semsarian, C; Reichlin, T; Barth, AS; Roden, DM; James, CA; Ware, JS; Chahal, CAA; Genotype‐First Approach Investigators |
| Publisher Information: |
American Heart Association |
| Publication Year: |
2024 |
| Collection: |
Queen Mary University of London: Queen Mary Research Online (QMRO) |
| Subject Terms: |
biobank; cardiac arrhythmia; cardiomyopathy; genetics; precision health; precision medicine sudden cardiac death; Humans; Cardiovascular Diseases; Genetic Testing; Genetic Predisposition to Disease; Precision Medicine; Genotype; Risk Assessment; Phenotype |
| 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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
e033557 - ? |
| Language: |
English |
| Relation: |
J Am Heart Assoc; https://qmro.qmul.ac.uk/xmlui/handle/123456789/103111 |
| DOI: |
10.1161/JAHA.123.033557 |
| Availability: |
https://qmro.qmul.ac.uk/xmlui/handle/123456789/103111; https://doi.org/10.1161/JAHA.123.033557 |
| Rights: |
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. ; © 2024 The Author(s). Published on behalf of the American Heart Association, Inc., by Wiley. |
| Accession Number: |
edsbas.430AD7A |
| Database: |
BASE |