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

英国南亚人的多重发病集群、轨迹和遗传风险

• 批准号: MR/S027297/1
• 负责人: Sarah Finer
• 金额: $ 64.43万
• 依托单位: Queen Mary University of London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FS027297%2F1
• 关键词: Multimorbidity; clusters; trajectories; genetic; risk

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.

我们的研究提案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多种健康状况影响的情况。研究表明，多种疾病在英国越来越普遍，而英国国家医疗服务体系 (NHS) 目前并没有专门设计的服务来很好地解决这一问题。最近的研究还表明，多种疾病以“集群”的形式存在，常见病症（例如 2 型糖尿病、高血压、慢性疼痛和抑郁症）常常同时存在。然而，关于多重疾病还有很多东西需要了解，需要更多的研究来找出它发生的原因、谁处于危险之中，以及如何设计更好的健康和社会护理来管理它。我们的提案将产生新的知识，填补我们对多重病的理解中的一些重要空白。我们将研究生活在伦敦东部 105 万人口中的人们的多重病，其中三分之一来自南亚族裔，生活在社会经济高度贫困中；已知两者都是多发病的危险因素。电子健康记录中收集的数据（例如，当您去看全科医生时做出的诊断或给予您的治疗）将用于告知我们该人群的多发病情况。我们将使用最先进的统计技术，利用这些数据来告诉我们哪些是东伦敦最常见的多发病“集群”，以及与白人相比，英国南亚人的这些疾病是否有所不同。利用历史记录，我们将研究一个人一生中多发病集群的模式、可能与其相关的风险因素以及它们对个体的影响有多严重。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发病的遗传原因。 ELGH 是一项针对居住在伦敦东部的英籍孟加拉人和巴基斯坦人的大型研究，已有 32,000 名志愿者参与其中。 ELGH 的志愿者已同意我们访问他们的电子健康记录，并使用捐赠给该研究的唾液样本来研究他们的基因。我们将研究个体遗传密码的差异是否与多种疾病的风险有关。我们将研究的一个特定的遗传密码变化被称为“自合性”，这种现象影响着这些父母亲缘关系很常见的种族群体中的一些人。自合性增加了从一个人的母亲和父亲遗传的基因拷贝相同的机会，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的自合性数量是否会影响一个人患多种疾病的风险。我们还将调查目前遗传和健康研究中一个主要感兴趣的领域，称为多基因风险评分（PRS）。这些分数识别出个体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研究，我们将做出更广泛的努力，调查其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，以便不存在数据安全问题，并确保所有数据都是使用适当的同意和信息治理程序收集的。我们预计我们的研究的影响将是广泛的，包括支持改善多发病的健康和社会护理，或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为我们的研究志愿者带来直接利益。

项目成果

Tracking trajectories of multiple long-term conditions using dynamic patient-cluster associations

使用动态患者集群关联跟踪多种长期病症的轨迹

• DOI: 10.1109/bigdata55660.2022.10021034
• 发表时间: 2022
• 作者: Kremer R

Influence of autozygosity on common disease risk across the phenotypic spectrum.

• DOI: 10.1016/j.cell.2023.08.028
• 发表时间: 2023-10-12
• 期刊: CELL
• 影响因子: 64.5
• 作者: Malawsky, Daniel S.;van Walree, Eva;Jacobs, Benjamin M.;Heng, Teng Hiang;Huang, Qin Qin;Sabir, Ataf H.;Rahman, Saadia;Sharif, Saghira Malik;Khan, Ahsan;Mirkov, Masa Umicevic;Kuwahara, Hiroyuki;Gao, Xin;Alkuraya, Fowzan S.;Posthuma, Danielle;Newman, William G.;Griffiths, Christopher J.;Mathur, Rohini;van Heel, David A.;Finer, Sarah;O'Connell, Jared;Martin, Hilary C.
• 通讯作者: Martin, Hilary C.

Transferability of genetic loci and polygenic scores for cardiometabolic traits in British Pakistani and Bangladeshi individuals.

• DOI: 10.1038/s41467-022-32095-5
• 发表时间: 2022-08-09
• 期刊: Nature communications
• 影响因子: 16.6

Influence of autozygosity on common disease risk across the phenotypic spectrum

自合性对整个表型谱中常见疾病风险的影响

• DOI: 10.1101/2023.02.01.23285346
• 发表时间: 2023
• 作者: Malawsky D