Nature genetics, 2021-02, Vol.53 (2), p.135-142
2021
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- Autor(en) / Beteiligte
- Titel
- Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity
- Ist Teil von
- Nature genetics, 2021-02, Vol.53 (2), p.135-142
- Ort / Verlag
- United States: Nature Publishing Group
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Hypertrophic cardiomyopathy (HCM) is a common, serious, genetic heart disorder. Rare pathogenic variants in sarcomere genes cause HCM, but with unexplained phenotypic heterogeneity. Moreover, most patients do not carry such variants. We report a genome-wide association study of 2,780 cases and 47,486 controls that identified 12 genome-wide-significant susceptibility loci for HCM. Single-nucleotide polymorphism heritability indicated a strong polygenic influence, especially for sarcomere-negative HCM (64% of cases; h = 0.34 ± 0.02). A genetic risk score showed substantial influence on the odds of HCM in a validation study, halving the odds in the lowest quintile and doubling them in the highest quintile, and also influenced phenotypic severity in sarcomere variant carriers. Mendelian randomization identified diastolic blood pressure (DBP) as a key modifiable risk factor for sarcomere-negative HCM, with a one standard deviation increase in DBP increasing the HCM risk fourfold. Common variants and modifiable risk factors have important roles in HCM that we suggest will be clinically actionable.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1061-4036eISSN: 1546-1718DOI: 10.1038/s41588-020-00764-0Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8240954
- Format
- –
- Schlagworte
- Adolescent, Adult, Aged, Blood pressure, Blood Pressure - genetics, Cardiac Myosins - genetics, Cardiomyopathy, Cardiomyopathy, Hypertrophic, Cardiomyopathy, Hypertrophic - genetics, Carrier Proteins - genetics, Case-Control Studies, Chromosomes, Formins - genetics, Genealogy, Genes, Genetic aspects, Genetic diversity, Genetic Predisposition to Disease, Genetic variance, Genetic variation, Genome-wide association studies, Genome-Wide Association Study, Genomes, Health aspects, Heritability, Heterogeneity, Heterozygote, Humans, Meta-analysis, Middle Aged, Mutation, Myosin Heavy Chains - genetics, Nucleotides, Polymorphism, Polymorphism, Single Nucleotide, Principal components analysis, Risk analysis, Risk Factors, Sarcomeres - genetics, Single-nucleotide polymorphism, Standard deviation, Young Adult