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Using genetics to understand how modifiable lifestyle changes may prevent disease in later life: A life course approach

利用遗传学来了解可改变的生活方式改变如何预防晚年疾病：生命全程方法

基本信息

批准号：
2470524
负责人：
金额：
--
依托单位：
University of Bristol
依托单位国家：
英国
项目类别：
Studentship
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=studentship-2470524
关键词：
Using genetics understand how modifiable

项目摘要

Understanding the manner in which modifiable factors (including lifestyle) during childhood and adolescence influence our risk of disease is challenging. For instance, individuals who are obese in early life have elevated risk of cardiovascular disease. However, as these individuals tend to remain obese into later life, it is unclear how much of this conferred risk can be reversed by making lifestyle changes. Furthermore, complex disease is typically determined by multiple risk factors, which may or may not act independently of one and other. This PhD will use large datasets to develop a putative causal map of how multiple lifestyle factors influence disease risk. There will be an emphasis on early life exposures, as results suggesting that conferred risk during childhood can be reversed will have an important translatable message that can impact social policy. Conversely, it is imperative to better understand which early life risk factors have an immutable influence on disease susceptibility which cannot be mitigated through lifestyle modifications. The principles of a technique in epidemiology known as Mendelian randomization (MR) will be applied. This approach uses genetics to disentangle causal relationships, which is particularly powerful given that our genes are inherited randomly at birth. As such they are robust to factors such as confounding and reverse causation which hinder observational analyses.

了解童年和青少年时期可改变的因素（包括生活方式）影响我们患病风险的方式是具有挑战性的。例如，早年肥胖的人患心血管疾病的风险较高。然而，由于这些人倾向于在以后的生活中保持肥胖，目前还不清楚这种风险在多大程度上可以通过改变生活方式来扭转。此外，复杂疾病通常由多个危险因素决定，这些因素可能独立于其中一个或另一个而起作用，也可能不独立于另一个。本博士将使用大型数据集来开发多种生活方式因素如何影响疾病风险的假定因果图。将强调早期生活暴露，因为研究结果表明，儿童时期赋予的风险可以逆转，这将具有重要的可翻译信息，可以影响社会政策。相反，必须更好地了解哪些早期生活风险因素对疾病易感性具有不可改变的影响，而这些影响不能通过改变生活方式来减轻。将应用流行病学中被称为孟德尔随机化（MR）的技术原理。这种方法利用遗传学来解开因果关系，考虑到我们的基因在出生时是随机遗传的，这种方法尤其强大。因此，他们是稳健的因素，如混淆和反向因果关系，阻碍观察分析。