Reassessment of genes associated with dilated and hypertrophic cardiomyopathy in a Chinese Han population

Introduction: More than 100 genes are reportedly associated with dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). However, the situation that many genes lack of reassessment in a large population hinders the interpretations of these genes in genetic diagnostic testing. Moreover, limited genetic data for cardiomyopathy in Chinese patients was reported. Aim: Therefore, here we reassessed an estimated 500 putative genes in the Chinese Han population by whole exome sequencing (WES) to describe the landscape of variants in these genes and to confirm their genetic contribution to DCM and HCM. Methods and Results: WES was performed in 1059 DCM patients, 1175 HCM patients and 514 controls. Approximately 500 candidate genes were selected for evaluation. Truncating variants of TTN and MYBPC3 were the most burdensome for both groups. Gene-based association tests identified 35 and 35 genes associated with DCM and HCM, respectively. Except for the known genes of cardiomyopathy, the top three genes associated with DCM were MUC16, KMT2C, and FBN1, while the top three genes associated with HCM were KMT2C, RYR2, and SCN5A. . After filtering for pathogenicity, FBN1 is still significantly associated with DCM and SCN5A and RYR2 remains significantly enriched in HCM patients. However, after adjustment, only TTN with DCM and MYBPC3 and MYH7 with HCM remains significant. Conclusion: We described the genetic landscape of Chinese patients with DCM and HCM and developed a website (www.cardioexome.cn) to enable open access to this information. Furthermore, the gene-based association test confirmed the contribution of TTN to DCM and MYBPC3 and MYH7 to HCM in Chinese Han. In addition, the website, www.cardioexome.cn, was developed to store these sequencing results.