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)调查乳制品摄入与心血管疾病风险因素的遗传变异之间的关系；2)获得特定的培训，建立合作关系并获得资金，以促进向独立研究者的过渡。研究目标将通过分析参与CHARGE（基因组流行病学心脏与衰老研究队列）联盟的研究数据来实现。培训目标将通过遗传学、高级统计分析和营养流行病学方面的正式培训、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。候选人的主要导师是Jose as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，共同导师团队包括心血管健康研究负责人兼医师研究员David Siscovick博士和Framingham心脏研究负责人兼遗传学统计学家Adrienne cuples博士。对乳制品的代谢反应，包括饱腹感、能量平衡、体重和预防糖尿病，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，但目前对这种独特食物组的建议对成年人来说是普遍适用的。该研究的具体目的是：1)研究与乳制品摄入量相互作用以改变身体的遗传因素

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.