Sex- and Smoking- Specific DNA Methylation Signatures of Central Adiposity Change

中枢性肥胖变化的性别和吸烟特异性 DNA 甲基化特征

• 批准号: 9513804
• 负责人: Anne Justice
• 金额: $ 24.81万
• 依托单位: GEISINGER CLINIC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9513804
• 关键词: Accounting; Address; African American; Age; Aging; Anthropology; Applications Grants; Atherosclerosis Risk in Communities; Behavior Therapy; Biological Markers; Body fat; Central obesity; Complex; DNA Methylation; Data; Data Analyses; Development; Diagnosis; Disease; Environment; Environmental Exposure; Environmental Risk Factor; Epidemiologist; Epigenetic Process; Ethnic Origin; European; Faculty; Foundations; Gender; Genes; Genetic; Genotype; Goals; Growth; Heart; Height; Hip region structure; Individual; International; Intervention; Lead; Link; Literature; Mentors; Methods; Methylation; Minority; Modeling; Morbidity - disease rate; National Heart, Lung, and Blood Institute; North Carolina; Nutritionist; Obesity; Other Genetics; Outcomes Research; Participant; Pathogenesis; Pharmaceutical Preparations; Pharmacogenomics; Phase; Phenotype; Physicians; Population; Population Genetics; Positioning Attribute; Postdoctoral Fellow; Predisposition; Public Health; Quantitative Trait Loci; Race; Research; Research Personnel; Research Project Grants; Risk; Risk Factors; Role; Secure; Smoking; Smoking Behavior; Strategic Planning; Talents; Time; Training; Translating; United States National Institutes of Health; Universities; Variant; Visit; analytical method; bead chip; biomarker identification; cardiometabolic risk; career; career development; clinically relevant; cohort; design; disorder risk; epigenetic marker; epigenetic variation; epigenome-wide association studies; epigenomics; experience; genetic epidemiology; genomic epidemiology; health disparity; innovation; knowledge base; mortality; obesity risk; obesogenic; outcome forecast; phenotypic data; programs; prospective test; public health relevance; sex; skills; waist circumference

 DESCRIPTION (provided by applicant): ABSTRACT Candidate: This is a NHLBI K99/R00 grant proposal, intended to promote my career as a post-doctoral fellow at the University of North Carolina, into independence as a genetic epidemiologist with a focus in obesity epigenetics. I am a trained anthropological geneticist with extensive experience in genetic epidemiology and a strong track record of innovative and informative research. Research and Career Goals: My over-arching research goal is to integrate my skills as an anthropologist, population geneticist, and epidemiologist, using the bio-cultural and public health perspectives to identify genetic, epigenetic and environmental factors that influence obesity and downstream cardiometabolic disease (CMD) across the lifecourse. Related to this, my long-term career goals include securing a faculty position at a research university where I will continue my research on the genetic and environmental factors that influence risk of CMD as an independent researcher and educator. Career Development: I will develop: 1) expertise in the pathogenesis of obesity, 2) a strong foundation in longitudinal data analysis, and 3) the theoretical and analytical skills specific for epigenetics research. My training and proposed research will be overseen by a talented group of mentors, including my primary mentor, Kari North, a renowned genetic epidemiologist that will provide expertise in integrating genetics and epigenetic analysis and methods; and my co-mentors, Penny Gordon-Larsen, a nutritionist and internationally recognized obesity expert; Yun Li, a biostatistician and geneticist with expertise in the development and application of analytical methods for genetics and epigenetics; Annie Green Howard, a biostatistician that specializes in longitudinal data analysis; Ellen Demerath, consultant, a lifecourse CMD epidemiologist with experience in methylation research; and Eric Whitsel, collaborator, a CVD epidemiologist and physician with experience in pharmacogenomics. Research Project: The proposed project aims to identify methylation variants (meQTLs) associated with increased central adiposity and for which the effects may be influenced by environmental exposures (sex, obesogenic medications, smoking) in the African American participants of the Atherosclerosis Risk in Communities (ARIC) study. In the K99 phase, I will conduct an epigenome wide association analysis (EWAS) with central adiposity using methylation data from a single time point and while accounting for environmental exposures. During the R00 phase, I will collect de novo methylation data using stored biospecimens from visit five to implement longitudinal, multilevel, and mixed models to examine differential epigenetic effects on central adiposity by age and time, and to examine the causal relationships between central adiposity change, methylation, and environmental exposures. Projects, like that proposed herein, allow us to identify epigenetic variation that influences central adiposity, and are critical to gain a comprehensive understanding of the pathogenesis of obesity. The results of this study and the continued protected training time will ultimately launch my career in lifecourse obesity epigenetics.

 描述（通过应用程序证明）：这是一个NHLBI K99/R00赠款提案，旨在促进我在北卡罗来纳州的Unighty的职业。是一个人类学的遗传学家，在遗传流行病学中曾经是遗传学的研究和研究和职业目标。在整个生活中，确定影响对衰落的遗传，表观遗传和环境因素（CMD）。肥胖发病机理的专业知识，2）纵向数据分析的强大基础，以及3）特定于表观遗传学研究的理学技能，包括我的主要导师Kari North，这是一位著名的遗传流行病学家Kari North遗传学分析和我的同事，一分钱戈登，痛苦的肥胖症专家，顾问，一名生命式CMD流行病学家，具有甲基化经验和Eric Whitsel，合作者，CVD流行病学家和具有药物基因组学经验的医师。在K99阶段，在社区中的非裔美国人（ARIC）研究中，肥胖的阳离子，吸烟）。 ntal暴露于肠道，并通过年龄和时间变化，甲基化和环境暴露对中央肥胖的差异影响，就像拟议中的re那能影响中心肥胖一样最终发射 我的生命肥胖表观遗传学的职业。