Translating genome-wide association data from the WTCCC study into biological and clinical insights in type 2 diabetes

在英国和其他地方，糖尿病是导致疾病和死亡的主要原因，而且还在不断增加。大多数成年后出现的糖尿病是由2型糖尿病引起的：世界上近10%的S人口要么患有这种疾病，要么将在他们的一生中患上这种疾病。尽管具有这种全球重要性，但对导致2型糖尿病发展的过程的了解还远未完成，需要做很多工作来开发更有效的预防和治疗方法。要更好地了解糖尿病，最有希望的途径之一是确定影响个体的基因--S患这种疾病的易感性。近年来，已经有了一些有希望的发展，已经发现了几个这样的基因。最近，随着人类基因组测序知识和技术的进步，在系统和全基因组中搜索这样的基因已经成为可能。时尚。这项提案的申请者目前正在完成这样的全基因组关联？研究(迄今对糖尿病遗传学进行的最大规模的研究)。对实验数据的分析将很快开始，并将为许多新的糖尿病基因的位置提供初步线索。然而，仍然需要大量的工作来区分由于偶然或错误而产生的真实影响和虚假发现，并毫无疑问地建立相关基因的身份。这项工作涉及进一步研究50,000个DNA样本，占据了我们研究计划的第一部分。有了这样一组已证实的糖尿病易感信号，我们的目标是将这些发现转化为对糖尿病生物学的更好理解。我们将以不同的方式做到这一点：例如，通过研究这些基因如何与环境因素(不良饮食、缺乏锻炼)相互作用来影响患糖尿病的风险。最后，我们想看看利用这些遗传信息来改善糖尿病的治疗和预防是否可行。我们会问，我们已经确定的遗传差异是否会让我们预测一个特定的人患糖尿病的可能性有多大，以及哪些治疗方法可能特别有益。这项工作将由牛津、埃克塞特和邓迪的团队进行，这些团队在过去十年里一直在共同努力，了解2型糖尿病的原因。所要求的资金将使他们能够在实现这一目标方面取得重大进展。

Diabetes is a major and growing cause of disease and death in the UK and beyond. Most diabetes arising after early adulthood is due to ?type 2 diabetes?: almost 10 percent of the world?s population either has this condition or will develop it during their lifetime. Despite this global importance, understanding of the processes which lead to development of type 2 diabetes is far from complete, and much needs to be done to develop more effective approaches to prevention and treatment. One of the most promising routes to a better understanding of diabetes comes from identifying the genes which influence an individual?s predisposition to develop the disease. In recent years, there have been some promising developments and several such genes have been identified. More recently, through advances in knowledge and technology that have followed the sequencing of the human genome, it has become possible to search for such genes in a systematic and ?genomewide? fashion. The applicants on this proposal are currently completing such a ?genomewide association? study (the largest yet conducted into the genetics of diabetes). Analysis of the experimental data will commence shortly and will provide initial clues to the locations of many novel diabetes genes. However, a great deal of work will still be required to separate real effects from spurious findings due to chance or error, and to establish beyond doubt the identities of the genes involved. This work, which involves studying a further 50,000 DNA samples, occupies the first part of our research proposal.With such a set of confirmed diabetes-susceptibility signals in hand, we aim to translate these discoveries into an improved understanding of the biology of diabetes. We will do this in various ways: for instance, by studying how these genes interact with environmental factors (poor diet, lack of exercise) to influence risk of diabetes. Finally, we want to see whether it is practical to use this genetic information to improve the treatment and prevention of diabetes. We will ask whether the genetic differences we have identified will allow us to predict how likely it is that a given individual will develop diabetes and which treatments may be particularly beneficial. The work will be performed by groups in Oxford, Exeter and Dundee who have spent the last decade working together to understand the causes of type 2 diabetes. The funding requested will enable them to make major strides towards this goal.