Multimorbidity clusters, trajectories and genetic risk, in British south Asians

我们的研究计划涵盖了一个重要的健康领域，称为“多重疾病”，它描述了一个人受到两种或两种以上健康状况的影响。研究表明，多重疾病在英国越来越普遍，而国民健康服务体系（NHS）目前并没有很好地解决这一问题的服务。最近的研究还表明，多病以“群集”形式存在，常见病症（如2型糖尿病、高血压、慢性疼痛和抑郁症）往往并存。然而，关于多重疾病还有很多需要了解的地方，需要更多的研究来找出它发生的原因，谁有风险，以及如何设计更好的卫生和社会保健来管理它。我们的建议将产生新的知识，填补我们对多病的理解中的一些重要空白。我们将研究居住在伦敦东部105万人口中的多病人群，其中三分之一来自南亚族裔，他们生活在高度的社会经济剥夺中；两者都是多重发病的危险因素。电子健康记录中收集的数据（例如，当您访问您的全科医生时所做的诊断或给予您的治疗）将用于告知我们该人群的多病情况。我们将使用最先进的统计技术，利用这些数据来告诉我们伦敦东部最常见的多病“集群”，以及与白人相比，英国南亚人是否有所不同。利用历史记录，我们将研究一个人一生中多病集群的模式，哪些风险因素可能与之相关，以及它们对个人的影响有多严重。我们研究的下一个重点将是利用参与东伦敦基因与健康（ELGH）研究的志愿者基因组的前沿研究来调查多病的遗传原因。ELGH是一项针对居住在伦敦东部的英国-孟加拉国和巴基斯坦裔人群的大型研究，已有3.2万名志愿者参与。ELGH的志愿者已经同意我们访问他们的电子健康记录，并使用捐赠给研究的唾液样本研究他们的基因。我们将研究个体遗传密码的差异是否与多病风险有关。我们将研究的一种特殊的遗传密码变化被称为“自合性”，这种现象影响了这些种族群体中的一些人，在这些种族群体中，父母的亲缘关系很普遍。自合子增加了从父母那里遗传的基因副本相同的几率，一些研究表明，这与某些疾病有关。我们将研究一个人的基因组成中自合子的数量是否会影响一个人患多种疾病的风险。我们还将调查目前在遗传和健康研究中主要感兴趣的领域，称为多基因风险评分（PRS）。这些分数可以识别出个人遗传密码的多个微小变化，当使用数学公式将这些变化加在一起时，可以有力地预测某人是否有患心脏病等疾病的风险。prs主要在白人群体中进行了研究，我们将为更广泛的努力做出贡献，以调查它们对南亚人疾病和多发病的影响。我们的研究将使用潜在的敏感数据，我们将采取非常严格和谨慎的方法来使用这些数据，以确保没有数据安全问题，并确保所有数据都是通过适当的同意和信息治理程序收集的。我们预计我们的研究将产生广泛的影响，包括支持改善对多种疾病的健康和社会护理，也许更有效地利用有限的NHS资金。我们将通过教育计划和公众参与，将直接利益回馈给我们的研究志愿者。

Our research proposal covers an important area of health called 'multimorbidity', which describes where an individual is affected by 2 or more health conditions. Studies have shown that multimorbidity is getting more common in the United Kingdom, and the National Health Service does (NHS) not currently have services designed to tackle it well. Recent research has also shown that multimorbidity exists in 'clusters', with groups of common conditions (e.g. type 2 diabetes, high blood pressure, chronic pain, and depression) often co-exist. However, there is a lot still to learn about multimorbidity, and more research is needed to find out why it occurs, who is at risk, and how to design better health and social care to manage it. Our proposal will produce new knowledge that fills some of the important gaps in our understanding of multimorbidity.We will study multimorbidity in people living in a large east London population of 1.05million people, one-third of whom come from a south Asian ethnic group and who live in high socioeconomic deprivation; both known to be risk factors for multimorbidity. Data collected in electronic health records (e.g. the diagnoses made or treatments given to you when you visit your GP) will be used to inform us about multimorbidity in this population. We will use state-of-the-art statistical techniques that use this data to tell us which are the most common 'clusters' of multimorbidity in east London, and whether they vary in British south Asians compared to Whites. Using historical records, we will study patterns of multimorbidity clusters during a person's life, what risk factors might be associated with them, and how severely they may impact an individual.The next focus in our research will be to investigate the genetic causes of multimorbidity using cutting edge studies of the genome in volunteers participating in the East London Genes and Health (ELGH) study. ELGH is a large study of people of British-Bangladeshi and -Pakistani origin living in east London, with 32,000 volunteers involved already. Volunteers in ELGH have given consent for us to access their electronic health records and also study their genes using a spit sample donated to the study. We will investigate whether differences in the genetic code of individuals are linked to the risk of multimorbidity. One specific genetic code change we will be looking at is called 'autozygosity', a phenomenon affecting some people in these ethnic groups where parental relatedness is common. Autozygosity increases the chance that gene copies inherited from a person's mother and father are the same, and some studies have shown that this is linked to certain disease. We will study whether the amount of autozygosity in a person's genetic make-up could affect a person's risk of developing multimorbidity. We will also investigate an area of major interest in genetic and health studies at the moment, called polygenic risk scores (PRS). These scores identify multiple, small changes to an individual's genetic code that, when added together using a mathematical formula, strongly predict whether someone is at risk of developing conditions such as heart disease. PRSs have been studied mostly in people of White ethnic groups, and we will contribute to wider efforts to investigate their impact on disease and multimorbidity in south Asians. Our research will use potentially sensitive data for our studies and we will take very stringent and careful approaches to using this data so that there are no data security issues, and to ensure all data has been collected using appropriate consent and information governance procedures.We expect that the impact of our research will be wide-ranging, including supporting improvements in health and social care for multimorbidity and perhaps more efficient use of limited NHS funds. We will deliver direct benefits back to our research volunteers through educational programmes and public engagement.