The penetrance of rare variants in cardiomyopathy-associated genes: A cross-sectional approach to estimating penetrance for secondary findings

McGurk, Kathryn A.; Zhang, Xiaolei; Theotokis, Pantazis; Thomson, Kate; Harper, Andrew; Buchan, Rachel J.; Mazaika, Erica; Ormondroyd, Elizabeth; Wright, William T.; Macaya, Daniela; Pua, Chee Jian; Funke, Birgit; MacArthur, Daniel G.; Prasad, Sanjay K.; Cook, Stuart A.; Allouba, Mona; Aguib, Yasmine; Yacoub, Magdi H.; O'Regan, Declan P.; Barton, Paul J.R.; Watkins, Hugh; Bottolo, Leonardo; Ware, James S.

doi:10.1016/j.ajhg.2023.08.003

Cited by 13 publications

(2 citation statements)

References 54 publications

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“…Whole-genome sequencing in population-scale biobanks such as Iceland (deCODE), FINNGEN, UK BioBank, and the Danish National Cohort Study (DANCOS) has led to the development of a number of techniques to identify cause–effect relationships between genetic signatures and phenotypes including genome-wide association studies (GWAS), phenome-wide association studies (PheWAS), and forward/reverse Mendelian randomization . For example, these methods have allowed for the characterization of rare genetic variants associated with health phenotypes such as the eye and cardiovascular diseases . In clinical cohorts, genomic data sets have been used to characterize mutational signatures underlying complex NCDs such as cancer .…”

Section: Opportunities To Integrate Exposome Research and Population ...mentioning

confidence: 99%

“… 66 For example, these methods have allowed for the characterization of rare genetic variants associated with health phenotypes such as the eye 67 and cardiovascular diseases. 68 In clinical cohorts, genomic data sets have been used to characterize mutational signatures underlying complex NCDs such as cancer. 69 Using GWAS, polygenic risk scores (PGSs) 70 , 71 are being adopted to predict relative likelihoods that an individual will acquire a disease based on genetic background alone.…”

Section: Opportunities To Integrate Exposome Research and Population ...mentioning

confidence: 99%

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Adopting Mechanistic Molecular Biology Approaches in Exposome Research for Causal Understanding

Foreman,

Warth,

Hessel

et al. 2024

Environ. Sci. Technol.

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Through investigating the combined impact of the environmental exposures experienced by an individual throughout their lifetime, exposome research provides opportunities to understand and mitigate negative health outcomes. While current exposome research is driven by epidemiological studies that identify associations between exposures and effects, new frameworks integrating more substantial population-level metadata, including electronic health and administrative records, will shed further light on characterizing environmental exposure risks. Molecular biology offers methods and concepts to study the biological and health impacts of exposomes in experimental and computational systems. Of particular importance is the growing use of omics readouts in epidemiological and clinical studies. This paper calls for the adoption of mechanistic molecular biology approaches in exposome research as an essential step in understanding the genotype and exposure interactions underlying human phenotypes. A series of recommendations are presented to make the necessary and appropriate steps to move from exposure association to causation, with a huge potential to inform precision medicine and population health. This includes establishing hypothesis-driven laboratory testing within the exposome field, supported by appropriate methods to read across from model systems research to human.

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Section: Opportunities To Integrate Exposome Research and Population ...mentioning

confidence: 99%

Section: Opportunities To Integrate Exposome Research and Population ...mentioning

confidence: 99%

Adopting Mechanistic Molecular Biology Approaches in Exposome Research for Causal Understanding

Foreman,

Warth,

Hessel

et al. 2024

Environ. Sci. Technol.

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Genetic testing and counseling for hypertrophic cardiomyopathy: An evidence‐based practice resource of the National Society of Genetic Counselors

Miller,

Brown,

Christian

et al. 2024

Journal of Genetic Counseling

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Hypertrophic cardiomyopathy (HCM) is a common hereditary condition affecting approximately 1 in 500 adults. It is characterized by marked clinical heterogeneity with individuals experiencing minimal to no symptoms, while others may have more severe outcomes including heart failure and sudden cardiac death. Genetic testing for HCM is increasingly available due to advances in DNA sequencing technologies and reduced costs. While a diagnosis of HCM is a well‐supported indication for genetic testing and genetic counseling, incorporation of genetic services into the clinical setting is often limited outside of expert centers. As genetic counseling and testing have become more accessible and convenient, optimal integration of genomic data into the clinical care of individuals with HCM should be instituted, including delivery via genetic counseling. Drawing on recommendations from recent disease guidelines and systematic evidence reviews, we highlight key recommendations for HCM genetic testing and counseling. This practice resource provides a comprehensive framework to guide healthcare providers in the process of genetic test selection, variant classification, and cascade testing for genetic evaluation of HCM.

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The Genetic Factors Influencing Cardiomyopathies and Heart Failure across the Allele Frequency Spectrum

Mukhopadhyay,

Dixit,

Khanom

et al. 2024

J. of Cardiovasc. Trans. Res.

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Heart failure (HF) remains a major cause of mortality and morbidity worldwide. Understanding the genetic basis of HF allows for the development of disease-modifying therapies, more appropriate risk stratification, and personalised management of patients. The advent of next-generation sequencing has enabled genome-wide association studies; moving beyond rare variants identified in a Mendelian fashion and detecting common DNA variants associated with disease. We summarise the latest GWAS and rare variant data on mixed and refined HF aetiologies, and cardiomyopathies. We describe the recent understanding of the functional impact of titin variants and highlight FHOD3 as a novel cardiomyopathy-associated gene. We describe future directions of research in this field and how genetic data can be leveraged to improve the care of patients with HF. Graphical Abstract

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The penetrance of rare variants in cardiomyopathy-associated genes: A cross-sectional approach to estimating penetrance for secondary findings

Cited by 13 publications

References 54 publications

Adopting Mechanistic Molecular Biology Approaches in Exposome Research for Causal Understanding

Adopting Mechanistic Molecular Biology Approaches in Exposome Research for Causal Understanding

Genetic testing and counseling for hypertrophic cardiomyopathy: An evidence‐based practice resource of the National Society of Genetic Counselors

The Genetic Factors Influencing Cardiomyopathies and Heart Failure across the Allele Frequency Spectrum

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