| Title: | Genetic architecture of hypertrophic cardiomyopathy in individuals of Chinese and United Kingdom ancestry |
| Journal: | Precision Clinical Medicine |
| Published: | 28 Jun 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40860236/ |
| DOI: | https://doi.org/10.1093/pcmedi/pbaf019 |
Publication 16480
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Abstract
Background: No studies have explored the genetic differences between the Chinese and other ethnic hypertrophic cardiomyopathy (HCM) populations.</p>
Methods: This cross-sectional study included Chinese patients (n = 593) with HCM and controls (n = 491) who underwent whole-exome sequencing. Rare variants in 16 validated HCM genes were assessed and compared with a United Kingdom HCM cohort (n = 1 232) and controls (n = 344 745).</p>
Results: Chinese HCM patients have a higher proportion of rare variants (52.8% vs 13.6%, P < 0.001) but have a similar proportion of pathogenic (P) or likely pathogenic (LP) variants compared to the UK cohort. In addition, the Chinese cohort had additional associations with the combined thin filament genes (P = 1.29E-9) and myosin light chain genes (P = 4.43E-3). The United Kingdom cohort was significantly associated with MYBPC3 non-truncating variants (P = 2.99E-7). By classifying variants using the tool genebe, the variants of uncertain significance were minimized to 46.8% compared to other tools (63.3% by Intervar; 91.3% by CardioClassifier). Furthermore, we report that c.3624del in MYBPC3 and c.300C > G in TNNT2 account for 2.9% and 1.5% of all Chinese HCM cases, respectively.</p>
Conclusion: Our findings suggested that patients of Chinese ancestry with HCM have a higher proportion of rare variants but are less likely to be classified as P/LP variants in HCM genes than those of European origin. The variants of c.3624del in MYBPC3 and c.300C > G in TNNT2 were specific to Chinese individuals and provide important insights into the ethnic differences of HCM genetic architecture.</p>
13 Authors
- Jie Wang
- Dominic Russ
- Yongsan Yang
- Lutong Pu
- Mengdi Yu
- Jinquan Zhang
- Jiajun Guo
- Yuanwei Xu
- Ke Wan
- Heng Xu
- Yuchi Han
- Georgios V Gkoutos
- Yucheng Chen
1 Application
| Application ID | Title |
|---|---|
| 31224 | Explanatory epidemiological models from genotype to phenotype |
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