Epigenomics of Cardiometabolic Diseases in Mexican Americans

墨西哥裔美国人心脏代谢疾病的表观基因组学

• 批准号: 9337499
• 负责人: Bertha Hidalgo
• 金额: $ 14.21万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9337499
• 关键词: Address; Adenine Nucleotides; Adult; Affect; Age; Aging; Blood Pressure; Body fat; Candidate Disease Gene; Cohort Analysis; Cohort Studies; Cytosine Nucleotides; DNA Methylation; Data; Data Set; Development; Diabetes Mellitus; Disease; Dyslipidemias; Environmental Exposure; Environmental Risk Factor; Epigenetic Process; Family; Fasting; Fostering; Gene Expression; Genes; Genetic; Genetic Polymorphism; Genomics; Glucose; Goals; Health; Health Care Costs; Heart; Heredity; Hispanics; Hypertension; Individual; Insulin; Investigation; K-Series Research Career Programs; Knowledge; Latino; Malignant Neoplasms; Mediator of activation protein; Mentors; Metabolic; Methods; Methylation; Mexican Americans; Modeling; Modification; Non-Insulin-Dependent Diabetes Mellitus; Nucleotides; Obesity; Outcome; Pathway interactions; Phenotype; Play; Positioning Attribute; Prevalence; Principal Investigator; Prospective cohort; Prospective cohort study; Regulation; Research; Research Training; Risk; Risk Factors; Role; Sampling; Scientist; Single Nucleotide Polymorphism; Site; Susceptibility Gene; Syndrome; TXNIP gene; Time; Triglycerides; Variant; Visit; causal model; comparative; design; epigenomics; fasting glucose; genome sequencing; genome-wide; health disparity; insight; methyl group; mortality; non-genetic; novel; programs; pyrosequencing; racial and ethnic; skills; trait; waist circumference; whole genome

 DESCRIPTION (provided by applicant): Cardiometabolic syndrome (CMS) is known as the collective impact of type 2 diabetes (T2D), hypertension (HTN), and obesity, and is one of the biggest health challenges facing the world today. DNA methylation, the addition of a methyl group to cytosine or adenine nucleotides, varies with aging and with environmental exposures, and is a critical epigenetic mediator of gene expression. CMS has a variety of local and systemic manifestations, all of which are likely impacted by a combination of genetic, genomic, and epigenetic pathways. We hypothesize that characterization of gene-specific DNA methylation marks will provide important insights into the factors contributing to CMS. We also hypothesize that characterizing DNA methylation marks correlated with ABCG1, CPT1A, and TXNIP variants may provide important insights into the regulation of these key cardiometabolic genes, previously determined to be important in CMS. Thus, the broad goals of this project include three specific aims to be carried out in the San Antonio Family Heart Study (SAFHS) cohort of 600 Mexican Americans: 1) To determine the association of quantitative methylation data from ABCG1, CPT1A, and TXNIP at baseline with prevalent diabetes-, hypertension-, and obesity-related phenotypes; 2) To determine the association of quantitative methylation data from ABCG1, CPT1A, and TXNIP at baseline with progression to diabetes, hypertension, and obesity over four study visits; and 3) To integrate single nucleotide polymorphism (SNP) variation, methylation marks, and gene expression data to define the most comprehensive causal model of CMS. The expected outcome of the proposed research and training is preliminary data to inform the design of a larger study led by the applicant to assess racial/ethnic variation in the epigenetics of CMS. In summary, this Mentored Career Development Award will foster the candidate's professional development as an independent scientist by providing an opportunity to gain expertise in epigenomics, health disparities, and statistical genetics. (End of Abstract)

 描述（由申请人提供）：心脏代谢综合征（CMS）被认为是 2 型糖尿病（T2D）、高血压（HTN）和肥胖的共同影响，是当今世界面临的最大健康挑战之一。 DNA 甲基化，即在胞嘧啶或腺嘌呤核苷酸上添加甲基，随着衰老和环境暴露而变化，是基因表达的关键表观遗传介质。 CMS 具有多种局部和全身表现，所有这些表现都可能受到遗传、基因组和表观遗传途径组合的影响。我们假设基因特异性 DNA 甲基化标记的表征将为 CMS 的影响因素提供重要的见解。我们还假设，表征与 ABCG1、CPT1A 和 TXNIP 变体相关的 DNA 甲基化标记可能为这些关键心脏代谢基因的调节提供重要见解，这些基因先前被确定在 CMS 中很重要。因此，该项目的总体目标包括在由 600 名墨西哥裔美国人组成的圣安东尼奥家庭心脏研究 (SAFHS) 队列中实现的三个具体目标： 1) 确定基线时 ABCG1、CPT1A 和 TXNIP 的定量甲基化数据与流行的糖尿病、高血压和肥胖相关表型的关联； 2) 确定基线时 ABCG1、CPT1A 和 TXNIP 的定量甲基化数据与四次研究访问中糖尿病、高血压和肥胖进展的关联； 3) 整合单核苷酸多态性 (SNP) 变异、甲基化标记和基因表达数据，定义最全面的 CMS 因果模型。拟议研究和培训的预期结果是初步数据，为申请人领导的一项更大规模研究的设计提供信息，以评估 CMS 表观遗传学的种族/民族变异。总之，该指导职业发展奖将通过提供获得表观基因组学、健康差异和统计遗传学方面的专业知识的机会，促进候选人作为独立科学家的专业发展。 （摘要完）