Interaction between diet and genetic variation: influence on Type 2 Diabetes risk

描述(由申请人提供)： 我们已经到达了遗传学和流行病学的新时代，研究与遗传学、环境和疾病有关的关键问题的资源广泛地提供给更广泛的研究社区。然而，很少有研究人员拥有充分利用这些资源所需的专业知识，这项建议的目的有两个：1)向在营养和心血管疾病流行病学领域拥有新兴专业知识的年轻研究人员提供遗传学和代谢紊乱领域的教学培训和指导；2)回答与遗传学和饮食对2型糖尿病(T2D)的集体影响相关的关键问题，长期目标是开发一个研究计划，继续战略性地消除该研究领域存在的层层复杂性。 遗传研究的最新进展导致发现了与T2D风险相关的常见遗传变异区域，并预示着在种群水平上可能产生重大影响。下一步是确定高遗传风险个体的最佳行动方案。饮食摄入量的整体表征，特别是特定食物类别和饮食模式的摄入量，在T2D的发展中发挥着重要作用。然而，我们还没有彻底探索这些关联是如何在具有T2D高遗传风险的人中发挥作用的。饮食被认为影响T2D风险的许多途径与那些被认为是受基因变异调节的途径是互补的。这项拟议研究的目的是确定目前已知的影响普通人群中T2D风险的饮食因素是否通过调节受遗传变异影响的互补代谢途径来改变基因和T2D之间的关联。我们将通过研究遗传变异和已知的影响T2D风险的食物之间的相互作用，以及已知的影响T2D风险的基因变异和饮食模式之间的相互作用来实现这一目标。该项目将利用候选基因关联资源(CARE)中包含的三个队列的数据：动脉粥样硬化多种族研究(MESA)、社区动脉粥样硬化风险(ARIC)研究和青年冠状动脉疾病风险(CARDIA)研究。

DESCRIPTION (provided by applicant): We have reached a new era in genetics and epidemiology where resources to study key questions related to genetics, environment, and disease are widely available to the greater research community. However, few researchers have the expertise needed to exploit these resources to their full potential, The aims of this proposal are two-fold: 1) to provide didactic training and mentorship in the fields of genetics and metabolic disorders to a young investigator with burgeoning expertise in the areas of nutrition and cardiovascular disease epidemiology, and 2) to answer key questions related to the collective influence of genetics and diet on type 2 diabetes (T2D) with the long term goal of developing a research program that will continue to strategically chip away the layers of complexity that exist in this area of research. Recent advances in genetic research have lead to the discovery of regions of common genetic variation that are associated withT2D risk and portend a potentially substantial impact at the population level. The next step is to determine the best course of action for individuals at high genetic risk. Holistic representations of dietary intake, specifically, intakes of particular food groups and dietary patterns, play an important role in the development of T2D. However, we have not thoroughly explored how these associations operate in persons with a high genetic risk for T2D. Many of the pathways by which diet is thought to influence T2D risk are complimentary to those thought to be modulated by genetic variation. The goal of the proposed research is to determine whether dietary factors currently known to influence risk of T2D in the general population modify associations between genotype and T2D by modulating complimentary metabolic pathways influenced by genetic variation. We will achieve this goal by studying interactions between genetic variation and foods known to influence T2D risk, as well as interactions between genetic variation and dietary patterns known to influence T2D risk. This project will utilize data from three cohorts included in the Candidate gene Association Resource (CARe): the Multi-Ethnic Study of Atherosclerosis (MESA), the Atherosclerosis Risk in Communities (ARIC) study, and the Coronary Artery disease Risk In young Adults (CARDIA) study.