Genetic Determinants of Taste Preferences and Risk of Metabolic Disease

描述（由申请人提供）：肥胖和2型糖尿病（T2 D）是日益增长的公共卫生问题。虽然饮食是一个众所周知的因素，在这些条件的发展，公共卫生的努力，饮食行为的修改已经遇到了有限的成功。苦，甜 和咸味偏好是饮食摄入的重要决定因素。味觉也可能发挥直接影响代谢健康的功能。因此，特定的口味偏好可能会影响肥胖和T2 D的风险，但支持这一观点的人类证据有限。在人群研究中，很少考虑个体间口味偏好的差异。这种变异的遗传决定因素的知识可以特别有用，在进一步了解我们的味觉生物学和阐明的作用，偏好苦，甜，或咸的食物可能在代谢疾病的发展。这些知识也可用于设计更有效的干预措施，以预防和治疗这些疾病。以前的研究旨在确定味觉基因位点，采取了生物学行为的方法来发现基因。随着遗传学领域的进步和大样本量的可用性，一种强大的、不可知的方法现在是可能的。然而，在大规模基于人群的研究中，口味偏好通常不会被测量;因此限制了对这些特征的传统和遗传流行病学研究。该提案的第一个目标是开发可以从现有食物偏好或消费数据中得出的口味偏好评分。我们的第二个目标是确定与人类味觉偏好相关的遗传位点，然后应用这些分子知识来破译味觉偏好在肥胖和T2 D发展中的作用。我们将使用根据食物消费数据和现有的全基因组扫描构建的味觉偏好评分，这些扫描可从基于人群的队列中获得：护士健康研究，健康专业人员随访研究和女性基因组健康研究。我们将在CHARGE联盟中复制最有希望的基因座，然后使用来自GIANT和DIAGRAM的可用结果来检查它们对肥胖和T2 D风险的影响;大型联盟分别致力于人体测量学和T2 D的遗传研究。通过结合先进的遗传知识和技术，复杂的统计工具，明确的特征和足够大的样本，我们的研究将为人类口味偏好的因素及其对肥胖和T2 D发展的影响提供新的见解。拟议的研究计划与NIDCD的味觉和味觉计划的优先事项I和III相一致：我们试图了解味觉偏好的“正常”变化以及这种变化如何在人群水平上影响代谢疾病。此外，这项研究的结果将促进新的研究路线，以减少饮食相关疾病的风险，并开发新的行为和药理学治疗和预防途径，从而间接解决该计划的第四个优先领域。

DESCRIPTION (provided by applicant): Obesity and type 2 diabetes (T2D) are growing public health concerns. Although diet is a well-known factor in the development of these conditions, public health efforts in dietary behavior modification have met with limited success. Bitter, sweet and salty taste preferences are important determinants of dietary intake. Taste may also serve functions that may directly impact metabolic health. Specific taste preferences might therefore impact risk of obesity and T2D, but human evidence supporting this notion is limited. Inter-individual variability in taste- preferences is rarely considered in population studies. Knowledge of the genetic determinants of this variation can be especially useful in furthering our understanding of taste biology and to elucidate the role that preferences for bitter, sweet, or salty foods may have in metabolic disease development. Such knowledge can also be used in designing more effective interventions for the prevention and treatment of these conditions. Previous studies aimed to identify taste genetic loci have taken a biology-to-behavior approach to gene discovery. A powerful, agnostic approach is now possible with advancements in the genetic field and the availability of large sample sizes. Taste preferences, however, are not commonly measured in large population-based studies; thus limiting both traditional and genetic epidemiological studies of these traits. The first goal of this proposal is to develop taste preference scores that can be derived from existing food preference or consumption data. Our second goal is to identify genetic loci associated with human taste preferences and then to apply this molecular knowledge to deciphering the role taste preferences play in obesity and T2D development. We will use taste preference scores constructed from food consumption data and existing genome-wide scans available from population-based cohorts: the Nurses' Health Study, Health Professionals Follow-up Study and the Women's Genome Health Study. We will replicate the most promising loci in the CHARGE consortium and then examine their impact on obesity and T2D risk using available results from GIANT and DIAGRAM; large consortia committed to the genetic study of anthropometry and T2D, respectively. By combining advanced genetic knowledge and technology, sophisticated statistical tools, a well-defined trait and a sufficiently sized sample, our research will provide novel insight into factors governing human taste preferences and the impact they have on obesity and T2D development. The proposed research plan aligns with Priorities I and III of NIDCD's Smell and Taste program: we seek to understand 'normal' variation in taste preference and how this variation impacts metabolic disease at a population level. Moreover, results of this study will foster new lines of investigatin for reducing risk of diet-related conditions and for developing novel behavioral and pharmacological avenues of treatment and prevention and thus indirectly addresses the program's fourth priority area.