image: In this cross-sectional study including 1 825 patients with HCM, Chinese patients have a higher proportion of rare variants but have a similar proportion of likely pathogenic or pathogenic variants compared with Europeans. In addition, c.3624del in MYBPC3 and c.300C>G in TNNT2 are predominantly present in patients of East Asian ancestry. In this study, ethnic disparities of HCM genetic architecture were observed, and a lack of prior research in Chinese populations limits variant interpretation in Chinese ancestry with HCM.
Credit: 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
Hypertrophic cardiomyopathy (HCM), a common genetic heart disorder, is often caused by mutations in sarcomere-related genes. While extensively studied in European populations, its genetic basis in Chinese individuals remains poorly understood.
In a groundbreaking cross-sectional study, researchers from West China Hospital and the University of Birmingham analyzed whole-exome sequencing data from 593 Chinese and 1,232 UK HCM patients, along with controls. They found that Chinese patients carry a significantly higher burden of rare variants (52.8% vs. 13.6% in the UK), yet the proportion of pathogenic or likely pathogenic (P/LP) variants was similar between the two groups.
Notably, two mutations—MYBPC3 c.3624del and TNNT2 c.300C>G—were identified as specific to the Chinese cohort, accounting for 2.9% and 1.5% of cases, respectively. The study also uncovered stronger associations with thin filament and myosin light chain genes in Chinese patients, while MYBPC3 non-truncating variants were more prominent in the UK cohort.
Using the tool genebe, researchers reduced the rate of variants of uncertain significance (VUS) to 46.8%, outperforming other classification tools and improving diagnostic clarity.
These findings underscore the importance of ethnicity-specific genetic databases and refined interpretation frameworks to avoid misclassification and enhance clinical management of HCM across diverse populations.
Journal
Precision Clinical Medicine
Method of Research
Experimental study
Subject of Research
Not applicable
Article Title
Genetic architecture of hypertrophic cardiomyopathy in individuals of Chinese and United Kingdom ancestry
Article Publication Date
24-Jul-2025