Genetic and Epigenetic Risk Scores for Chronic Kidney Disease in African Americans

非裔美国人慢性肾脏病的遗传和表观遗传风险评分

基本信息

批准号：
10446992
负责人：
Alana Christine Jones
金额：
$ 4万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10446992
关键词：
APOL1 gene Accounting Adult Affect African American population African ancestry Albuminuria Alcohols Algorithms Area Bioinformatics Biological Calibration Cardiovascular Diseases Cause of Death Chronic Kidney Failure Clinical Code Conscious Cytosine DNA Methylation Data Development Discrimination Disease Disease Management Disease Outcome Doctor of Philosophy End stage renal failure Environment Environmental Risk Factor Epidemiologic Methods Epidemiology Epigenetic Process Equation European Evaluation Exhibits Exposure to Familiarity Foundations Gene Expression Genetic Genetic Markers Genetic Risk Genome Genomics Goals Grant Guanine Health Policy Heritability Incidence Individual Jackson Heart Study Journals Kidney Learning Skill Link Linkage Disequilibrium Literature Manuscripts Mentors Methodology Methods Methylation Minority Groups Modeling Modification Neighborhoods Outcome Patients Performance Persons Physicians Pollution Population Prevalence Prevention Publishing Race Research Research Proposals Risk Risk Marker Scientist Severities Single Nucleotide Polymorphism Site Smoking Solid Statistical Methods Structural Racism Testing Time Training Translating Translational Research United States National Institutes of Health Variant Writing adverse outcome base burden of illness cardiovascular health cardiovascular risk factor career career development clinical application cohort disease disparity disease phenotype disorder prevention disorder risk epigenetic marker epigenome epigenome-wide association studies experience genetic epidemiology genetic variant genome wide association study genome-wide health disparity high risk improved inorganic phosphate interest mortality novel polygenic risk score prediction algorithm prevent racial disparity racism research and development responsible research conduct risk prediction risk stratification risk variant skills tool trait treatment strategy

项目摘要

PROJECT SUMMARY/ABSTRACT The purpose of this NIH F31-Diversity application is to obtain support for the PI, Alana Jones, for mentored research and career development activities within her MD/PhD degree training that will strengthen her potential to become an independent physician-scientist. The project goal is to develop skills in genetic epidemiology and bioinformatics that will allow her to identify genetic and epigenetic risk markers, as well as develop polygenic and methylation risk scores for chronic kidney disease (CKD) in African Americans (Aims 1 and 2), who experience disproportionately higher incidence and prevalence of disease. Additionally, she will test the utility of these scores in predicting adverse outcomes associated with CKD, particularly end-stage renal disease (ESRD) (Aim 3). These methods include genome-wide and epigenome-wide association studies, multivariate regression modeling, and risk score calibration and discrimination (e.g., C statistic). The primary objective of this research proposal is to identify individual markers for CKD and consolidate them into a prediction algorithm. CKD impacts 14% of the US population and is steadily rising as a major cause of mortality globally. As CKD is asymptomatic in ~90% of people until advanced stages, early risk stratification may be critical to preventing clinical sequelae, such as ESRD. The central hypothesis is that polygenic and methylation scores may be able to predict biological CKD risk and its associated outcomes, as both genetic and epigenetic variants contribute to the heritability of CKD. The long-term objective of her research is to understand how heritable factors influence health disparities and to develop clinical tools that guide treatment strategies. The proposed training plan for the PI is sponsored by her project mentor, Dr. Marguerite (Ryan) Irvin. Included in the training plan are experiences to help the PI develop in the following major areas: 1) rigorous research in the CKD field, including developing familiarity with the existing literature on CKD epidemiology and disparities, principles of scientific integrity and responsible conduct of research, and the application of genetic risk prediction for CKD outcomes; 2) genetic epidemiology, including methodology, interpretation of results, and critical evaluation of published polygenic and methylation risk scores; and 3) career and professional development, including learning skills in manuscript and grant writing, journal review, data presentation, and translation of research findings to clinical application. The overall goal of the training plan is to provide the PI with a solid foundation for a career as an independent physician-scientist, with the ultimate goal of leading a collaborative research team that bridges the gap between research on determinants of health disparities and the implementation of health policy in order to improve cardiovascular health outcomes.

项目摘要/摘要该NIH F31多样性应用的目的是获得对PI Alana Jones的支持在她的医学博士学位/博士学位培训中指导的研究和职业发展活动将增强她成为独立医师科学家的潜力。项目目标是发展遗传的技能流行病学和生物信息学将使她能够识别遗传和表观遗传风险标志物以及在非洲裔美国人中开发慢性肾脏疾病（CKD）的多基因和甲基化风险评分（目标1 2），他们的发病率和患病率不成比例。此外，她将测试这些分数在预测与CKD相关的不良后果方面的实用性，尤其是终端肾脏疾病（ESRD）（目标3）。这些方法包括全基因组和全基因组的关联研究，多元回归建模以及风险评分校准和歧视（例如C统计）。主要该研究建议的目的是确定CKD的个别标记，并将其巩固为预测算法。 CKD影响了美国人口的14％，并且稳步上升是全球死亡率的主要原因。由于CKD在约90％的人中是无症状的，直到高级阶段，因此早期风险分层可能对预防临床后遗症，例如ESRD。中心假设是多基因和甲基化评分可能能够预测生物CKD风险及其相关结果，因为遗传和表观遗传变异有助于CKD的遗传力。她的研究的长期目标是了解如何遗传因素影响健康差异并开发指导治疗策略的临床工具。 PI的拟议培训计划由她的项目导师Marguerite（Ryan）Irvin赞助。培训计划中包括在以下主要领域中帮助PI发展的经验：1）严格 CKD领域的研究，包括对CKD流行病学和现有文献熟悉差异，科学完整性原则和负责任的研究以及遗传的应用 CKD结果的风险预测； 2）遗传流行病学，包括方法论，结果解释和对已发表的多基因和甲基化风险评分评估的批判性评估； 3）职业和专业开发，包括手稿和赠款写作技巧，期刊评论，数据演示和将研究结果转换为临床应用。培训计划的总体目标是提供PI 以稳固的身份成为独立医师科学家的职业生涯，其最终目标是领导A 协作研究团队弥合了关于健康差异决定因素的研究与实施卫生政策，以改善心血管健康成果。