Genetic predictors of metabolic responses to dairy

描述(由申请人提供)：拟议的五年职业发展项目的长期目标是1)调查乳制品摄入量与心血管疾病风险因素基因变异之间的关系，2)获得具体培训，形成合作关系并获得资金，以促进过渡到独立研究人员。研究目标将通过对参加CHARD(基因组流行病学心脏和衰老研究队列)联盟的研究数据进行分析来实现。培训目标将通过遗传学、高级统计分析和营养流行病学的正式培训、参加研讨会和会议以及营养基因组学、心血管流行病学和统计遗传学方面的杰出科学家的指导来实现。这位候选人的主要导师是何塞·奥多瓦斯博士，他是心脏代谢风险基因-环境相互作用领域的先驱和国际领导者。为了促进候选人的职业发展，联合导师团队包括心血管健康研究负责人兼医生兼研究员David Siscovick博士和弗雷明翰心脏研究负责人兼遗传学统计学家Adrienne Cupples博士。对乳制品的代谢反应，包括饱腹感、能量平衡、体重和对糖尿病的保护，是不一致的，这种不一致可能反映了遗传变异。尽管存在这种差异，但目前对这一独特食物组的推荐对成年人来说是普遍的。这项拟议的研究的具体目的是：1)调查与乳制品摄入量相互作用的遗传因素，以改变身体 体重和葡萄糖代谢；2)研究这些遗传变异的潜在功能。为了实现这些目标，我们将使用全基因组方法来检测相关的遗传变异。外显子组分析和生物信息学将被应用于确定潜在的功能变异的子集，这些变异将在独立的种群中复制。分析将在欧洲血统的队列中进行，并在参与负责人的非裔美国人中进行，这是一个国际联盟，拥有丰富的基因型、深层表型和详细的饮食数据。塔夫茨大学将进行全面的职业发展和培训，这是一个拥有肥胖症、遗传学、糖尿病、流行病学和生物统计学专业知识的合作研究环境。候选人和主要导师位于美国农业部塔夫茨的Jean Mayer人类营养老龄化中心。课程将包括荟萃分析、微阵列数据分析、基因表达和表观基因组学。追求研究项目的具体目标以及遗传学和高级数据分析方面的培训计划，将有助于向独立研究过渡。对于乳制品和类似的广泛消费的食品，研究基因-环境相互作用的重大收获在于它们有可能澄清疾病机制，还在于它们转化为通过有针对性的生活方式改变来预防疾病的遗传知情饮食建议。

DESCRIPTION (provided by applicant): The longterm objectives of the proposed five year career development project are to 1) investigate relationships between dairy food intake and genetic variants for cardiovascular disease risk factors and 2) to gain specific training, form collaborative relationships and obtain funding in order to facilitate transition to an independent investigator. The research objectives will be achieved through analysis of data from studies participating in the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. The training objectives will be met through formal training in genetics, advanced statistical analysis and nutritional epidemiology, participation in seminars and meetings, and guidance by exceptional scientists in nutrigenomics, cardiovascular epidemiology and statistical genetics. The candidate's primary mentor is Dr. Jose Ordovas, a pioneer and international leader in the field of gene-environment interactions for cardio- metabolic risk. To enhance the career development of the candidate, the co-mentor team includes Dr. David Siscovick, Cardiovascular Health Study leader and physician-researcher, and Dr. Adrienne Cupples, Framingham Heart Study leader and genetics statistician. Metabolic responses to dairy foods, including satiety, energy balance, body weight and protection from diabetes, are inconsistent, and this inconsistency likely reflects genetic variability. In spite of this variability, current detary recommendations for this unique food group are universal for adults. The specific aims of the proposed study are to 1) investigate genetic factors that interact with dairy intake to modify body weight and glucose metabolism and 2) to investigate potential functionality of these genetic variants. To achieve these aims, we will use a genome-wide approach to detect relevant genetic variants. Exomic analyses and bioinformatics will be applied to identify a subset of potentially functional variants that will be replicated in independent populations. Analyses will be conducted in cohorts of European origin and in African Americans participating in CHARGE, an international consortium for which a wealth of genotypes, deep phenotypes and detailed dietary data are available. Comprehensive career development and training will be carried out at Tufts University, a collaborative research environment with expertise in obesity, genetics, diabetes, epidemiology and biostatistics. The candidate and primary mentor are located at the Jean Mayer USDA Human Nutrition Center on Aging at Tufts. Courses will include Meta- analysis, Microarray Data Analysis, Gene Expression, and Epigenomics. The pursuit of the specific aims of the research project and the training plan in genetics and advanced data analysis will facilitate transition to independent research. Substantial gains from studying gene-environment interactions, for dairy and similarly widely-consumed foods, lie in their potential for clarifying disease mechanisms, and also in their translation to genetically informed dietary recommendations that prevent disease through targeted lifestyle modification.