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：
10626909
负责人：
Alana Christine Jones
金额：
$ 4.92万
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/10626909
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 Conscious Cytosine DNA Methylation Data Development Discrimination Disease Disease Management Disease Outcome Disparity 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 Goals Grant Guanine Health Policy Heritability Incidence Individual Jackson Heart Study Journals Kidney Kidney Diseases 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 Factors Risk Marker Scientist Severities Single Nucleotide Polymorphism Site Smoking Solid Statistical Methods Structural Racism Testing Training Translating Translational Research United States National Institutes of Health Variant Writing adverse outcome 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 genomic predictors health determinants health disparity high risk improved inorganic phosphate interest mortality novel polygenic risk score prediction algorithm predictive tools prevent racial disparity racism research and development responsible research conduct risk prediction risk stratification risk variant segregation skills statistics structural determinants 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.

项目概要/摘要此 NIH F31-Diversity 申请的目的是获得对 PI Alana Jones 的支持，在她的医学博士/博士学位培训中指导研究和职业发展活动，这将增强她的能力成为独立医师科学家的潜力。该项目的目标是培养遗传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记，以及制定非裔美国人慢性肾病 (CKD) 的多基因和甲基化风险评分（目标 1 2）他们的疾病发病率和患病率不成比例地较高。此外，她还将测试这些评分在预测与 CKD（特别是终末期肾病）相关的不良后果方面的效用疾病 (ESRD)（目标 3）。这些方法包括全基因组和表观基因组关联研究，多元回归模型，以及风险评分校准和区分（例如，C 统计量）。初级该研究计划的目标是确定 CKD 的个体标记并将其整合为预测算法。 CKD 影响着 14% 的美国人口，并且正在稳步上升，成为全球死亡率的主要原因。由于约 90% 的人在晚期之前 CKD 都没有症状，因此早期风险分层可能对于预防临床后遗症，如 ESRD。中心假设是多基因和甲基化评分或许能够预测 CKD 的生物风险及其相关结果，因为遗传和表观遗传变异有助于 CKD 的遗传性。她研究的长期目标是了解遗传性如何影响健康差异的因素并开发指导治疗策略的临床工具。 PI 拟议的培训计划由她的项目导师 Marguerite (Ryan) Irvin 博士赞助。培训计划中包括帮助 PI 在以下主要领域发展的经验： 1) 严格 CKD 领域的研究，包括熟悉 CKD 流行病学的现有文献和差异、科学诚信原则和负责任的研究行为以及遗传的应用 CKD 结果的风险预测； 2) 遗传流行病学，包括方法、结果解释，以及对已发表的多基因和甲基化风险评分进行严格评估； 3）职业和专业发展，包括学习手稿和拨款写作、期刊评论、数据演示和将研究成果转化为临床应用。培训计划的总体目标是提供PI 为独立医师科学家的职业生涯奠定坚实的基础，最终目标是领导合作研究团队，旨在弥合健康差异决定因素研究与健康差异决定因素研究之间的差距实施卫生政策，以改善心血管健康结果。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Genetic Contributors of Efficacy and Adverse Metabolic Effects of Chlorthalidone in African Americans from the Genetics of Hypertension Associated Treatments (GenHAT) Study.

DOI：
10.3390/genes13071260
发表时间：
2022-07-15
期刊：
GENES
影响因子：
3.5
作者：
Armstrong, Nicole D.;Srinivasasainagendra, Vinodh;Chekka, Lakshmi Manasa S.;Nguyen, Nam H. K.;Nahid, Noor A.;Jones, Alana C.;Tanner, Rikki M.;Hidalgo, Bertha A.;Limdi, Nita A.;Claas, Steven A.;Gong, Yan;McDonough, Caitrin W.;Cooper-DeHoff, Rhonda M.;Johnson, Julie A.;Tiwari, Hemant K.;Arnett, Donna K.;Irvin, Marguerite R.
通讯作者：
Irvin, Marguerite R.

Differentially Methylated DNA Regions and Left Ventricular Hypertrophy in African Americans: A HyperGEN Study.