Background:No studies have explored the genetic differences between the Chinese and other ethnic hypertrophic cardiomyopathy(HCM)populations.Methods:This cross-sectional study included Chinese patients(n=593)with HCM ...Background:No studies have explored the genetic differences between the Chinese and other ethnic hypertrophic cardiomyopathy(HCM)populations.Methods:This cross-sectional study included Chinese patients(n=593)with HCM and controls(n=491)who underwent whole-exomesequencing.Rare variants in 16 validated HCM genes were assessed and compared with a United Kingdom HCM cohort(n=1232)and controls(n=344745).Results:Chinese HCM patients have a higher proportion of rare variants(52.8%vs 13.6%,P<0.001)but have a similar proportion ofpathogenic(P)or likely pathogenic(LP)variants compared to the UK cohort.In addition,the Chinese cohort had additional associationswith the combined thin filament genes(P=1.29E−9)and myosin light chain genes(P=4.43E−3).The United Kingdom cohort wassignificantly associated with MYBPC3 non-truncating variants(P=2.99E−7).By classifying variants using the tool genebe,the variantsof 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.Conclusion:Our findings suggested that patients of Chinese ancestry with HCM have a higher proportion of rare variants but are lesslikely 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>Gin TNNT2 were specific to Chinese individuals and provide important insights into the ethnic differences of HCM genetic architecture.展开更多
基金supported by grants from the Natural ScienceFoundation of China(grant No.82202248)the Natural ScienceFoundation of Sichuan Province(grant No.23NSFSC4589)+8 种基金1·3·5 projects for Artificial Intelligence,West China Hospital,Sichuan University(grant No.ZYAI24003)support from the NIHR Birmingham HPRU,NIHR Birmingham BRC,Nanocommons H2020-EU(731032)MAESTRIA(grant agreement ID 965286)CRUCK(PRCNPG-Nov23/100001)HYPERMARKER(grant agreement ID 101095480)PARC(grantAgreement No 101057014)the MRC Heath Data ResearchUK(HDRUK/CFC/01)HDRUK midlands regional communityproject(QQ2)initiatives funded by UK Research and Innovation,Department of Health and Social Care(England)and the devolved administrations,and leading medical research charities.
文摘Background:No studies have explored the genetic differences between the Chinese and other ethnic hypertrophic cardiomyopathy(HCM)populations.Methods:This cross-sectional study included Chinese patients(n=593)with HCM and controls(n=491)who underwent whole-exomesequencing.Rare variants in 16 validated HCM genes were assessed and compared with a United Kingdom HCM cohort(n=1232)and controls(n=344745).Results:Chinese HCM patients have a higher proportion of rare variants(52.8%vs 13.6%,P<0.001)but have a similar proportion ofpathogenic(P)or likely pathogenic(LP)variants compared to the UK cohort.In addition,the Chinese cohort had additional associationswith the combined thin filament genes(P=1.29E−9)and myosin light chain genes(P=4.43E−3).The United Kingdom cohort wassignificantly associated with MYBPC3 non-truncating variants(P=2.99E−7).By classifying variants using the tool genebe,the variantsof 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.Conclusion:Our findings suggested that patients of Chinese ancestry with HCM have a higher proportion of rare variants but are lesslikely 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>Gin TNNT2 were specific to Chinese individuals and provide important insights into the ethnic differences of HCM genetic architecture.
