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The Interactive Roles of Neighborhood Characteristics and Genetic Risk in Racial Inequalities in CKD

社区特征和遗传风险在 CKD 种族不平等中的相互作用

基本信息

批准号：
10226394
负责人：
Margaret Takako Hicken
金额：
$ 5.26万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
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：
2016-08-31 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10226394
关键词：
APOL1 gene Address African Apolipoproteins Area Biological Sciences Censuses Characteristics Chronic Kidney Failure Clinical Collaborations Complement Data Data Set Development Disease Education Educational workshop Empirical Research End stage renal failure Environment Epidemiology Ethnic Origin Faculty Foundations Functional disorder Genetic Genetic Predisposition to Disease Genetic Risk Genotype Goals Government Agencies Health Health Services Accessibility Health and Retirement Study Healthcare Income Inequality Institutes Institution Interdisciplinary Study International Intervention Kidney Kidney Diseases Link Measures Medical Genetics Mentorship Multi-Ethnic Study of Atherosclerosis Neighborhoods Nephrology Nephrotic Syndrome Outcome Patient Self-Report Persons Physiology Policies Population Population Genetics Predisposition Privatization Public Health Schools Race Renal function Research Research Personnel Research Project Grants Resources Risk Risk Factors Role Science Science of genetics Social Environment Social Sciences Solid Sorting - Cell Movement Source Training Variant Work beta Globin built environment career cohort disorder risk experience genetic epidemiology genetic risk factor genetic variant health inequalities high risk low socioeconomic status renal damage risk variant segregation social symposium

项目摘要

ABSTRACT: Racial inequalities in kidney and end stage renal diseases (ESRD) have been well-documented and are independent of lower socioeconomic status (e.g., income, education), lower access to care, or other conventional risk factors. Research has identified numerous genetic risk factors of renal disease, particularly the APOL1 variants occurring in persons of African descent. However, these genetic factors primarily increase susceptibility, requiring other factors for the development of disease. A growing body of research indicates the importance of neighborhoods for health and health inequalities. Unequal neighborhood contexts may be an important and largely unexplored determinant of the increased kidney disease risk experienced by Blacks compared to Whites. In fact, neighborhood context may interact with genetic susceptibility to result in kidney disease inequalities. Clarifying the role of neighborhood is important as neighborhoods are neither random nor naturally-occurring. They develop and change through policies and are thus amenable to intervention. Despite the evidence indicating the importance of neighborhoods for the major risk factors and determinants of kidney disease, there is a dearth of empirical research on the role of neighborhoods in relation to kidney disease itself, particularly at pre-ESRD stages. The primary challenges to research in this area are: (a) the lack of skilled researchers with training in both social science and the pathophysiology and genetic science of kidney disease; and (b) the paucity of datasets that contain high quality neighborhood and clinical and genetic measures. To reach my long-term career goal to become a successful, independent researcher who clarifies the social causes and genetic and biomedical mechanisms of racial CKD inequalities, I will address the current scientific challenges through the proposed training and research, respectively by: (a) complementing my early work in the biological sciences and extensive training in the social sciences with extensive training in the pathophysiology and genetics of kidney disease; and (b) creating state-of-the-art neighborhood measures to existing datasets with high quality repeat clinical measures of renal function and damage. I will address three career goals: 1. To obtain formal training in renal physiology and pathophysiology. 2. To develop expertise in genetic epidemiology and population genetics pertaining to racial inequalities in kidney disease. 3. To take the first step toward independence through an R01 submission. My training will include mentorship and collaboration with leading experts in the genetics and pathophysiology of CKD inequalities, formal coursework in genetic epidemiology, statistical/population genetics, and renal physiology/pathophysiology, and multiple conferences and workshops on the substantive topics of genetics, race, and CKD and on professional development. Through my research project, I will use three cohorts (Health and Retirement Study, Multi-Ethnic Study of Atherosclerosis, and Nephrotic Syndrome Study Network) to examine the interactive associations between multiple measures of four neighborhood domains (racial residential segregation, social environment, built environment, and health care resources) and genetic risk (APOL1 and β-globin HBB genotypes, adjusting for genetic ancestry), as follows: Aim 1: Link state-of-the-art measures of four domains of neighborhood context to population-representative, epidemiological, and clinical cohort datasets containing markers of kidney disease. Aim 2: Examine longitudinal associations between neighborhood context and renal health, with adjustment for genetic ancestry and APOL1 genotype. Aim 3: Examine the modifying role of neighborhood context on longitudinal associations between APOL1 high-risk genotype status and renal health. With this training and dataset creation, I will then clarify the neighborhood characteristics that are most tightly linked to renal outcomes both directly and through their interactions with genetic risk loci. This research will set a solid foundation for research on neighborhood characteristics and inequalities in kidney disease. Not only will this research clarify the interdependent roles of neighborhood and genetic risk on these inequalities, but it will identify key neighborhood characteristics, which are amenable to change, related to kidney disease within and between racial groups. UM is the ideal venue for my training and research as it is internationally recognized as a leading research institution that strongly supports interdisciplinary science. I joined the faculty both at the Institute for Social Research (ISR) because of its commitment to interdisciplinary research, and Nephrology because of its commitment to clarifying the social exposures that contribute to kidney disease. Within ISR, the Nephrology Division, and School of Public Health, I will acquire rigorous training and develop solid collaborations devoted to the clarification of the social and genetic causes of racial inequalities in CKD.

摘要：肾脏和终末期肾病 (ESRD) 方面的种族不平等已得到充分记录并且独立于较低的社会经济地位（例如收入、教育）、较低的护理机会或其他常规危险因素。研究已经确定了许多肾脏疾病的遗传风险因素，特别是 APOL1 变异发生在非洲人后裔中。然而，这些遗传因素主要增加易感性，疾病的发展需要其他因素。越来越多的研究表明社区对于健康和健康不平等的重要性。不平等的邻里环境可能是导致人口增加的一个重要且很大程度上尚未被探索的决定因素。与白人相比，黑人患肾脏疾病的风险更高。事实上，邻里环境可能会相互作用具有导致肾脏疾病不平等的遗传易感性。明确邻里关系的角色这很重要，因为邻里既不是随机的也不是自然发生的。他们通过以下方式发展和改变政策，因此容易受到干预。尽管有证据表明对于肾脏疾病的主要危险因素和决定因素，目前缺乏实证研究研究社区在肾脏疾病本身中的作用，特别是在终末期肾病（ESRD）前期阶段。这该领域研究面临的主要挑战是：(a) 缺乏接受过社会和社会两方面培训的熟练研究人员肾脏疾病的科学、病理生理学和遗传科学； (b) 数据集的缺乏包含高质量的邻里、临床和遗传测量。为了实现我的长期职业目标，成为一名成功的、独立的研究员，阐明社会问题种族 CKD 不平等的原因以及遗传和生物医学机制，我将讨论当前的科学问题通过拟议的培训和研究来应对挑战，分别是：(a) 补充我在生物科学和社会科学领域的广泛培训肾脏疾病的病理生理学和遗传学； (b) 制定最先进的邻里措施具有高质量重复临床肾功能和损伤测量的现有数据集。我将阐述三个职业目标： 1. 获得肾脏生理学和病理生理学方面的正式培训。 2. 发展与种族不平等有关的遗传流行病学和群体遗传学专业知识肾脏疾病。 3. 通过提交 R01 迈出走向独立的第一步。我的培训将包括与遗传学和病理生理学领域领先专家的指导和合作 CKD 不平等、遗传流行病学、统计/群体遗传学和肾病的正式课程生理学/病理生理学，以及关于遗传学实质性主题的多个会议和研讨会，种族、CKD 和职业发展。通过我的研究项目，我将使用三个队列（健康与退休研究、多种族研究动脉粥样硬化和肾病综合征研究网络）来检查之间的相互作用四个邻里领域的多重衡量标准（种族居住隔离、社会环境、建筑环境和医疗保健资源）和遗传风险（APOL1 和 β-珠蛋白 HBB 基因型，调整为遗传血统），如下：目标 1：将邻里环境四个领域的最先进测量方法与人口代表性、包含肾脏疾病标志物的流行病学和临床队列数据集。目标 2：检查邻里环境与肾脏健康之间的纵向关联，并进行调整用于遗传血统和 APOL1 基因型。目标 3：检查邻里环境对 APOL1 之间纵向关联的修改作用高风险基因型状态和肾脏健康。通过这种训练和数据集创建，我将阐明最紧密的邻里特征直接或通过与遗传风险位点的相互作用与肾脏结果相关。这项研究将设定为研究肾脏疾病的邻里特征和不平等奠定了坚实的基础。不仅会这项研究阐明了邻里关系和遗传风险对这些不平等的相互依存作用，但它将确定与肾脏疾病相关的、易于改变的关键社区特征种族群体之间。密歇根大学是我进行培训和研究的理想场所，因为它是国际公认的领先研究机构大力支持跨学科科学的机构。我加入了社会研究所的教员研究 (ISR) 因其致力于跨学科研究，而肾病学因其致力于跨学科研究致力于澄清导致肾脏疾病的社会暴露。在 ISR 中，肾脏病学我部和公共卫生学院将接受严格的培训并开展牢固的合作致力于澄清慢性肾病种族不平等的社会和遗传原因。