PDF(Pubmed)
Abstract：
Left ventricular maximum wall thickness (LVMWT) is an important biomarker of left ventricular hypertrophy and provides diagnostic and prognostic information in hypertrophic cardiomyopathy (HCM). Limited information is available on the genetic determinants of LVMWT.
We performed a genome-wide association study of LVMWT measured from the cardiovascular magnetic resonance examinations of 42 176 European individuals. We evaluated the genetic relationship between LVMWT and HCM by performing pairwise analysis using the data from the Hypertrophic Cardiomyopathy Registry in which the controls were randomly selected from UK Biobank individuals not included in the cardiovascular magnetic resonance sub-study.
Twenty-one genetic loci were discovered at P<5×10-8. Several novel candidate genes were identified including PROX1, PXN, and PTK2, with known functional roles in myocardial growth and sarcomere organization. The LVMWT genetic risk score is predictive of HCM in the Hypertrophic Cardiomyopathy Registry (odds ratio per SD: 1.18 [95% CI, 1.13-1.23]) with pairwise analyses demonstrating a moderate genetic correlation (rg=0.53) and substantial loci overlap (19/21).
Our findings provide novel insights into the genetic underpinning of LVMWT and highlight its shared genetic background with HCM, supporting future endeavours to elucidate the genetic etiology of HCM.
We performed a genome-wide association study of LVMWT measured from the cardiovascular magnetic resonance examinations of 42 176 European individuals. We evaluated the genetic relationship between LVMWT and HCM by performing pairwise analysis using the data from the Hypertrophic Cardiomyopathy Registry in which the controls were randomly selected from UK Biobank individuals not included in the cardiovascular magnetic resonance sub-study.
Twenty-one genetic loci were discovered at P<5×10-8. Several novel candidate genes were identified including PROX1, PXN, and PTK2, with known functional roles in myocardial growth and sarcomere organization. The LVMWT genetic risk score is predictive of HCM in the Hypertrophic Cardiomyopathy Registry (odds ratio per SD: 1.18 [95% CI, 1.13-1.23]) with pairwise analyses demonstrating a moderate genetic correlation (rg=0.53) and substantial loci overlap (19/21).
Our findings provide novel insights into the genetic underpinning of LVMWT and highlight its shared genetic background with HCM, supporting future endeavours to elucidate the genetic etiology of HCM.
摘要：
背景：左心室最大壁厚度（LVMWT）是左心室肥厚的重要生物标志物，并在肥厚型心肌病（HCM）中提供诊断和预后信息。关于LVMWT的遗传决定因素的信息有限。
方法：我们对LVMWT进行了全基因组关联研究，该研究通过42176名欧洲个体的心血管磁共振检查进行测量。我们通过使用肥厚型心肌病注册中心的数据进行成对分析，评估了LVMWT和HCM之间的遗传关系，其中对照组是从未包括在心血管磁共振子研究中的UKBiobank个体中随机选择的。
结果：在P<5×10-8发现了21个遗传基因座。鉴定了几个新的候选基因，包括PROX1，PXN，和PTK2，在心肌生长和肌节组织中具有已知的功能作用。LVMWT遗传风险评分可预测肥厚型心肌病注册中的HCM（每SD的比值比：1.18[95％CI，1.13-1.23]），配对分析表明中度遗传相关性（rg=S0.53）和大量基因座重叠（19/21）。
结论：我们的发现为LVMWT的遗传基础提供了新的见解，并强调了其与HCM的共同遗传背景，支持未来努力阐明HCM的遗传病因。
方法：我们对LVMWT进行了全基因组关联研究，该研究通过42176名欧洲个体的心血管磁共振检查进行测量。我们通过使用肥厚型心肌病注册中心的数据进行成对分析，评估了LVMWT和HCM之间的遗传关系，其中对照组是从未包括在心血管磁共振子研究中的UKBiobank个体中随机选择的。
结果：在P<5×10-8发现了21个遗传基因座。鉴定了几个新的候选基因，包括PROX1，PXN，和PTK2，在心肌生长和肌节组织中具有已知的功能作用。LVMWT遗传风险评分可预测肥厚型心肌病注册中的HCM（每SD的比值比：1.18[95％CI，1.13-1.23]），配对分析表明中度遗传相关性（rg=S0.53）和大量基因座重叠（19/21）。
结论：我们的发现为LVMWT的遗传基础提供了新的见解，并强调了其与HCM的共同遗传背景，支持未来努力阐明HCM的遗传病因。
