The genetic aetiology of hypertropic cardiomyopathy

肥厚性心肌病(HCM)是一种遗传性心血管疾病，每500人中就有1人受到影响，是导致心脏性猝死的主要原因。虽然传统上被认为是一种单基因、常染色体显性疾病，但目前的临床基因检测策略无法解释大多数(~60%)的HCM病例。在招募了许多患有这种疾病(n=10,000)和没有患这种疾病(n=&gt；100,000)的人之后，我的研究使用了统计和计算方法的组合，以更好地了解肥厚性心肌炎的遗传基础，并为MRC战略技能优先事项(长寿和健康生活：分子数据集和疾病)做出贡献。这促进了我之前在临床医学、计算生物学和统计学方面的培训，提供了尖端临床统计和生物信息技术(Farrall教授)以及临床研究和分子生物学(Watkins教授)方面的培训。因此，这实现了MRC概述的跨学科交叉技能主题。作为国际合作者网络的一部分，我将利用现有的下一代测序数据，寻求提供强有力的统计证据来支持或驳斥支持HCM的拟议遗传模型。此外，我的工作将集中在与HCM相关的变异对“正常”人群心肌功能的影响上。这将加深我们对心肌生物学的理解，有助于阐明潜在的疾病机制，我们希望这将提高我们对肥厚性心肌炎的病理生理学的理解，并促进改善患者的护理。

Hypertrophic cardiomyopathy (HCM) is an inherited cardiovascular condition that affects 1 in 500 individuals and is a leading cause of sudden cardiac death. Whilst traditionally considered to be a monogenic, autosomal dominant condition, current clinical genetic testing strategies fail to explain most (~60%) cases of HCM. Following the recruitment of many individuals with (n= >10,000) and without the disease (n= >100,000), my research uses a combination of statistical and computational approaches to better understand the genetic basis of HCM and contributes to an MRC strategic skill priority (Living a long & healthy life: Molecular datasets and disease). This advances my previous training within clinical medicine, computational biology and statistics, by providing training in cutting-edge clinical statistics and bioinformatic techniques (Professor Farrall) and clinical research and molecular biology (Professor Watkins). Consequently, this fulfills a cross-cutting interdisciplinary skills theme outlined by the MRC. As part of an international network of collaborators, I will look to provide robust statistical evidence to either support or refute proposed inheritance models underpinning HCM, using available next-generation sequencing data. In addition, my work will focus on the impact variants associated with HCM have upon heart muscle function within the 'normal' population. This will refine our understanding of myocardial biology and contribute towards the elucidation of underlying disease mechanisms, which we hope will improve our understanding of the pathophysiology of HCM and facilitate improved patient care.