Understanding disease through environment-wide association studies

每个人的疾病风险既受遗传因素的影响，也受其环境的影响。环境因素包括，例如，暴露于外部风险因素，如接触杀虫剂，以及行为暴露，如吸烟或健身习惯。对于许多疾病，个体疾病风险的大部分差异被认为是由于环境因素的差异。此外，与无法控制的遗传因素不同，暴露在环境风险中的风险可以减少，为疾病预防提供了一条途径，特别是对于遗传风险较高的个人。虽然已经确定了一些疾病的主要环境风险因素，例如吸烟和肺癌之间的联系，但大多数环境因素可能只有很小的影响，许多这样的因素共同作用于疾病风险。该项目的目的是开发方法和计算工具，以便能够在大群体中确定这种小到中等的环境风险因素。使用在英国生物库的大约500,000名参与者中测量的1000多个环境因素，我们将应用这些方法来识别与心肌梗死(心脏病发作)和中风相关的因素，这两个因素是英国的两大主要死亡原因。该项目的结果可能有助于制定关于人们接触的环境因素和他们的生活方式选择的具体建议，例如降低他们心脏病发作和中风的风险。已识别的风险因素还可以提供有关这些疾病所涉及的途径的信息，帮助我们更好地了解疾病是如何发展的。更广泛地说，开发的方法和工具将广泛适用于其他疾病，并将使我们能够创建更好的个人风险概况，从而更好地分配用于疾病监测和预防的资源。

The disease risk for each individual is influenced by both genetic factors and their environment. Environmental factors encompass, for instance, exposures to external risk factors, like, e.g., exposure to pesticides, and behavioral exposures, like, e.g., smoking or fitness habits. For many diseases a majority of the variation in individual disease risk is thought to be due to differences in environmental factors. Furthermore unlike genetic factors, which cannot be controlled, exposure to environmental risks can be moderated providing a pathway to disease prevention, in particular for individuals with elevated genetic risk. While for some diseases major environmental risk factors have been identified, like, e.g., the link between smoking and lung cancer, most environmental factors are likely to have small effects, with many such factors jointly acting on disease risk. This project aims to develop methods and computational tools which will make it possible to identify such small to moderate environmental risk factors in large cohorts. Using over a thousand environmental factors measured in about 500,000 participants of the UK Biobank, we will apply these methods to identify factors which are associated with myocardial infarction (heart attack) and stroke, two of the leading causes of death in the UK. The results from this projects could help in developing concrete recommendations regarding environmental factors people are exposed to and their lifestyles choices such as to lower their risk of heart attacks and stroke. Identified risk factors could also provide information about pathways involved in these diseases, helping us to better understand how the disease develops. More generally, the developed of methods and tools will be widely applicable to other disease and will allow us to create better individual risk profiles allowing for better allocation of resources for disease monitoring and prevention.