| Title: | Evaluation of polygenic scores for hypertrophic cardiomyopathy in the general population and across clinical settings |
| Journal: | Nature Genetics |
| Published: | 18 Feb 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39966645/ |
| DOI: | https://doi.org/10.1038/s41588-025-02094-5 |
| URL: | https://kclpure.kcl.ac.uk/portal/en/publications/f9859b42-c611-425a-9c31-e875d93da74d |
Publication 15265
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Abstract
Hypertrophic cardiomyopathy (HCM) is an important cause of morbidity and mortality, with pathogenic variants found in about a third of cases. Large-scale genome-wide association studies (GWAS) demonstrate that common genetic variation contributes to HCM risk. Here we derive polygenic scores (PGS) from HCM GWAS and genetically correlated traits and test their performance in the UK Biobank, 100,000 Genomes Project, and clinical cohorts. We show that higher PGS significantly increases the risk of HCM in the general population, particularly among pathogenic variant carriers, where HCM penetrance differs 10-fold between those in the highest and lowest PGS quintiles. Among relatives of HCM probands, PGS stratifies risks of developing HCM and adverse outcomes. Finally, among HCM cases, PGS strongly predicts the risk of adverse outcomes and death. These findings support the broad utility of PGS across clinical settings, enabling tailored screening and surveillance and stratification of risk of adverse outcomes.</p>
12 Keywords
- Adult
- Cardiomyopathy, Hypertrophic
- Female
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Male
- Middle Aged
- Multifactorial Inheritance
- Penetrance
- Polymorphism, Single Nucleotide
- United Kingdom
38 Authors
- Sean L. Zheng
- Sean J. Jurgens
- Kathryn A. McGurk
- Xiao Xu
- Chris Grace
- Pantazis I. Theotokis
- Rachel J. Buchan
- Catherine Francis
- Antonio de Marvao
- Lara Curran
- Wenjia Bai
- Chee Jian Pua
- Hak Chiaw Tang
- Paloma Jorda
- Marjon A. van Slegtenhorst
- Judith M. A. Verhagen
- Andrew R. Harper
- Elizabeth Ormondroyd
- Calvin W. L. Chin
- Antonis Pantazis
- John Baksi
- Brian P. Halliday
- Paul Matthews
- Yigal M. Pinto
- Roddy Walsh
- Ahmad S. Amin
- Arthur A. M. Wilde
- Stuart A. Cook
- Sanjay K. Prasad
- Paul J. R. Barton
- Declan P. O'Regan
- R. T. Lumbers
- Anuj Goel
- Rafik Tadros
- Michelle Michels
- Hugh Watkins
- Connie R. Bezzina
- James S. Ware
1 Application
| Application ID | Title |
|---|---|
| 47602 | Understanding the genetic architecture of inherited cardiovascular conditions (ICCs) and cardio-renal disease |
Enabling scientific discoveries that improve human health