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

基本信息

批准号：
9754860
负责人：
Anne Justice
金额：
$ 24.84万
依托单位：
GEISINGER CLINIC
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2021-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9754860
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 cardiometabolism career career development clinically relevant cohort design 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

项目摘要

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（由申请人提供）：摘要候选人：这是 NHLBI K99/R00 拨款提案，旨在促进我作为北卡罗来纳大学博士后研究员的职业生涯，成为一名独立的遗传流行病学家，重点研究肥胖表观遗传学我是一名训练有素的人类遗传学家，在遗传流行病学方面拥有丰富的经验，并且在整合创新和信息研究和职业目标方面拥有良好的记录：我的总体研究目标是我的目标。作为人类学家、人口遗传学家和流行病学家的技能，利用生物文化和公共卫生的视角来识别肥胖影响整个生命过程的遗传、表观遗传和环境因素以及与此相关的下游心脏代谢疾病（CMD）。职业目标包括在一所研究型大学获得教职，作为一名独立研究员和教育者，我将继续研究影响 CMD 风险的遗传和环境因素：我将发展：1）肥胖发病机制方面的专业知识。 , 2）在纵向数据分析方面有坚实的基础，3）表观遗传学研究的理论和分析技能将由一群才华横溢的导师监督，其中包括我的主要导师，著名的遗传流行病学家卡里·诺斯（Kari North）。将提供整合遗传学和表观遗传学分析和方法的专业知识；以及我的共同导师 Penny Gordon-Larsen，她是一位营养学家和国际公认的肥胖专家 Yun Li，她是一位生物统计学家和遗传学家，在开发和应用方面具有专业知识；遗传学和表观遗传学分析方法；Annie Green Howard，一位专门从事纵向数据分析的生物统计学家；Ellen Demerath，一位具有甲基化研究经验的生命全程 CMD 流行病学家；以及 Eric Whitsel，一位合作者、一位 CVD 流行病学家和具有药物基因组学经验的医生；研究项目：拟议项目旨在识别与中央肥胖增加相关的甲基化变异（meQTL），其影响可能受到环境暴露（性别、在 K99 阶段，我将使用单个时间点和同时的甲基化数据对中枢性肥胖进行表观基因组广泛关联分析 (EWAS)。在 R00 阶段，我将使用第五次访问中存储的生物样本收集从头甲基化数据，以实施纵向、多层次和混合模型，以检查对中枢的差异表观遗传影响。按年龄和时间划分的肥胖，并检查中枢性肥胖变化、甲基化和环境暴露之间的因果关系。像本文提出的项目，使我们能够识别影响中枢性肥胖的表观遗传变异，这对于全面了解中枢性肥胖至关重要。肥胖发病机制的研究结果和持续保护训练时间最终将展开。我的职业生涯是肥胖表观遗传学。