Understanding disease through environment-wide association studies

每个人的患病风险受到遗传因素和环境的双重影响。环境因素包括，例如，暴露于外部风险因素，例如，暴露于杀虫剂，以及行为暴露，例如，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，暴露于环境风险是可以缓和的，这为预防疾病提供了途径，特别是对遗传风险较高的个人而言。虽然已经确定了某些疾病的主要环境风险因素，例如吸烟与肺癌之间的联系，但大多数环境因素的影响可能很小，许多这类因素共同作用于疾病风险。这个项目的目的是开发方法和计算工具，以便能够在大型队列中确定这种小到中等的环境风险因素。使用在英国生物银行约50万参与者中测量的一千多个环境因素，我们将应用这些方法来确定与心肌梗死（心脏病发作）和中风相关的因素，这是英国死亡的两个主要原因。这些项目的结果可以帮助制定具体的建议，包括人们接触的环境因素和他们的生活方式选择，比如降低心脏病发作和中风的风险。确定的风险因素还可以提供与这些疾病有关的途径的信息，帮助我们更好地了解疾病的发展。更一般地说，所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.