英国伦敦帝国理工学院James S. Ware团队的一项最新研究提出了在普通人群和临床环境中评估肥厚型心肌病的多基因评分。2025年2月18日，国际知名学术期刊《自然—遗传学》发表了这一成果。

在这里，该研究团队从HCM GWAS和遗传相关性状中获得多基因评分（PGS），并在UK Biobank、100000基因组计划和临床队列中测试它们的表现。课题组发现，较高的PGS显著增加了一般人群中HCM的风险，特别是在致病变异携带者中，在PGS最高和最低五分之一的人群中，HCM外显率相差10倍。在HCM先证亲属中，PGS对HCM发生风险和不良结局进行分层。最后，在HCM病例中，PGS强烈预测不良结局和死亡的风险。这些发现支持了PGS在临床环境中的广泛应用，可以进行量身定制的筛查、监测和不良后果风险分层。

据介绍，肥厚性心肌病（HCM）是一个重要的发病率和死亡率的主题，在大约三分之一的病例中发现致病性变异。大规模全基因组关联研究（GWAS）表明，常见的遗传变异与HCM风险有关。

附：英文原文

Title: Evaluation of polygenic scores for hypertrophic cardiomyopathy in the general population and across clinical settings

Author: Zheng, Sean L., Jurgens, Sean J., McGurk, Kathryn A., Xu, Xiao, Grace, Chris, Theotokis, Pantazis I., Buchan, Rachel J., Francis, Catherine, de Marvao, Antonio, Curran, Lara, Bai, Wenjia, Pua, Chee Jian, Tang, Hak Chiaw, Jorda, Paloma, van Slegtenhorst, Marjon A., Verhagen, Judith M. A., Harper, Andrew R., Ormondroyd, Elizabeth, Chin, Calvin W. L., Pantazis, Antonis, Baksi, John, Halliday, Brian P., Matthews, Paul, Pinto, Yigal M., Walsh, Roddy, Amin, Ahmad S., Wilde, Arthur A. M., Cook, Stuart A., Prasad, Sanjay K., Barton, Paul J. R., ORegan, Declan P., Lumbers, R. T., Goel, Anuj, Tadros, Rafik, Michels, Michelle, Watkins, Hugh, Bezzina, Connie R., Ware, James S.

Issue&Volume: 2025-02-18

Abstract: Hypertrophic cardiomyopathy (HCM) is an important cause of morbidity and mortality, with pathogenic variants found in about a third of cases. Large-scale genome-wide association studies (GWAS) demonstrate that common genetic variation contributes to HCM risk. Here we derive polygenic scores (PGS) from HCM GWAS and genetically correlated traits and test their performance in the UK Biobank, 100,000 Genomes Project, and clinical cohorts. We show that higher PGS significantly increases the risk of HCM in the general population, particularly among pathogenic variant carriers, where HCM penetrance differs 10-fold between those in the highest and lowest PGS quintiles. Among relatives of HCM probands, PGS stratifies risks of developing HCM and adverse outcomes. Finally, among HCM cases, PGS strongly predicts the risk of adverse outcomes and death. These findings support the broad utility of PGS across clinical settings, enabling tailored screening and surveillance and stratification of risk of adverse outcomes.

DOI: 10.1038/s41588-025-02094-5

Source: https://www.nature.com/articles/s41588-025-02094-5