Physical Frailty in Urban African-Americans

城市非裔美国人的身体虚弱

• 批准号: 7624550
• 负责人: Victor G. Davila-Roman
• 金额: $ 37.99万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7624550
• 关键词: Abbreviations; Accounting; Address; African American; Aging; American; Applications Grants; Area; Arts; Behavioral; Blood Vessels; Candidate Disease Gene; Cardiac; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Cessation of life; Cities; Collaborations; Communities; Complex; Coronary Arteriosclerosis; Data; Data Collection; Development; Disease; Enrollment; Environment; Epidemiology; Face; Factor Analysis; Frequencies; Functional disorder; Funding; Genes; Genetic; Genetic Polymorphism; Genotype; Haplotypes; Health; Heart Diseases; Heart failure; Image; Imaging Techniques; Inflammatory; Lead; Left; Left Ventricular Hypertrophy; Left ventricular structure; Life; Linear Models; Major Depressive Disorder; Mediating; Methods; Missouri; Molecular; Morbidity - disease rate; Mutation Analysis; Myocardial Infarction; Not Hispanic or Latino; Organ; Pathway Analysis; Pathway interactions; Phenotype; Population; Population Study; Prevalence; Process; Recording of previous events; Recruitment Activity; Research; Research Personnel; Risk; Role; Sampling; Serotonin; Slice; Source; Statistical Methods; Techniques; Testing; United States National Institutes of Health; Universities; Ventricular; Washington; aged; base; cardiovascular imaging; clinically relevant; cohort; computer based statistical methods; depression; depressive symptoms; design; detector; disability; disease phenotype; disorder risk; endophenotype; frailty; genetic analysis; genetic association; genetic profiling; genetic variant; genome wide association study; genome-wide; health disparity; independent component analysis; innovation; mortality; multidisciplinary; non-genetic; novel; population based; prevent; public health relevance; response; serotonin transporter; social; tool; trait; translational study

DESCRIPTION (provided by applicant): This NIH Revision application for Physical Frailty in Urban African Americans (PFUAA; AG10436) responds to PAR-08-065. It requests 3 years of funding to enable additional data collection on a representative well-characterized cohort of African Americans living in St. Louis, MO, (the African American Health project, or AAH). Data to be collected relate to potential interactions between genetic factors and depression in mediating coronary artery disease (CAD) risk in AAH using single SNP/haplotype association analyses. CAD is the leading cause of cardiovascular morbidity and mortality in the U.S. Nationally, African Americans have higher morbidity-mortality rates from CAD than whites, and particularly so in Missouri and in the city of St. Louis. Depression is also common and has multiple adverse associations with CAD. These relationships have been understudied in population-based samples and especially in African Americans. As frailty and disability are associated with both atherosclerotic disease and depressive symptoms, better understanding of the genetic reasons for the adverse CAD-depression associations is crucial to the AAH project. Prior data indicate that these conditions are common in AAH, with 3-year period prevalences of 42% for cardiovascular diseases and 31% for clinically relevant levels of depressive symptoms. Despite the well-known CAD-depression adverse associations, the precise genetic factors and molecular mechanisms mediating them remain largely unknown. The overarching hypothesis of this project is that depression contributes to the development and sequelae of CAD through common gene-gene (GXG) and/or gene-environment (GXE) interactions. To examine this hypothesis, this NIH Revision project will enroll 450 AAH subjects to pursue three specific aims: SA1. Identify the prevalence of CAD and depression phenotypes in a population-based sample of community-dwelling 57-75 year old African Americans. SA2. Examine the relationships between the CAD and depression phenotypes in this population, highlighting the modulating role of selected genes in the serotonin and inflammatory pathways. SA3. Discover potential gene-depression interactions with significant contribution to the development of CAD in African Americans. We have assembled an outstanding multidisciplinary group with all the required expertise to conduct this research, including epidemiology (aging, depression, cardiovascular, and genetic), cardiac imaging, CAD and depression phenotyping, cardiovascular disease mutation analysis, and (crucially) the development and use of novel statistical methods to study genetic polymorphisms for translational studies of cardiovascular disease. We plan to follow this project with a larger grant application to recruit 1050 additional subjects and perform genome wide analyses to address these important issues in even greater depth. This research has the potential to identify excellent targets for pharmacological and non-pharmacological approaches to preventing, ameliorating, or reversing either or both of these important conditions. PUBLIC HEALTH RELEVANCE: Coronary artery disease is a leading cause of death and health problems in the U.S. and has a particularly strong impact on African Americans. The presence of depression increases the frequency of coronary artery disease and all its complications in both blacks and whites. The purpose of this research is to examine the relationship between coronary artery disease and depression in an ongoing study of African Americans living in St. Louis, Missouri with an emphasis on understanding how genetic factors interact with depression symptoms to exert such a strong negative impact on coronary artery disease.

描述（由申请人提供）：本NIH修订版城市非裔美国人身体虚弱申请（PFUAA; AG 10436）响应PAR-08-065。它要求3年的资金，以使更多的数据收集的代表性良好的特征队列的非洲裔美国人生活在圣路易斯，密苏里州，（非洲裔美国人健康项目，或AAH）。采用单核苷酸多态性/单倍型关联分析，收集的数据涉及遗传因素和抑郁症在介导AAH患者冠状动脉疾病（CAD）风险方面的潜在相互作用。CAD是美国心血管发病率和死亡率的主要原因。在全国范围内，非裔美国人的CAD发病率-死亡率高于白人，尤其是在密苏里州和圣路易斯市。抑郁症也很常见，与CAD有多种不良关系。这些关系在基于人群的样本中，特别是在非洲裔美国人中，研究得不够。由于虚弱和残疾与动脉粥样硬化性疾病和抑郁症状相关，因此更好地了解不良CAD-抑郁关联的遗传原因对AAH项目至关重要。先前的数据表明，这些情况在AAH中很常见，3年期间心血管疾病的患病率为42%，临床相关抑郁症状水平的患病率为31%。尽管众所周知的CAD抑郁症的不良关联，精确的遗传因素和分子机制介导他们仍然在很大程度上是未知的。该项目的总体假设是抑郁症通过共同基因-基因（GXG）和/或基因-环境（GXE）相互作用促进CAD的发展和后遗症。为了检验这一假设，NIH修订项目将招募450名AAH受试者，以实现三个特定目标：在社区居住的57-75岁非裔美国人中确定CAD和抑郁症表型的患病率。SA 2.检查该人群中CAD和抑郁症表型之间的关系，突出选择的基因在5-羟色胺和炎症通路中的调节作用。SA 3.发现潜在的基因-抑郁相互作用，对非裔美国人CAD的发展有重大贡献。我们已经组建了一个优秀的多学科小组，拥有开展这项研究所需的所有专业知识，包括流行病学（衰老，抑郁症，心血管和遗传），心脏成像，CAD和抑郁症表型，心血管疾病突变分析，以及（至关重要的）开发和使用新的统计方法来研究遗传多态性，用于心血管疾病的转化研究。我们计划在这个项目之后，申请更大的资助，招募1050名额外的受试者，并进行全基因组分析，以更深入地解决这些重要问题。这项研究有可能确定药理学和非药理学方法的优良靶点，以预防，改善或逆转这些重要疾病中的一种或两种。公共卫生关系：冠状动脉疾病是美国死亡和健康问题的主要原因，对非洲裔美国人的影响尤其严重。抑郁症的存在增加了黑人和白人冠状动脉疾病及其所有并发症的发生率。本研究的目的是在一项正在进行的对居住在密苏里州圣路易斯的非裔美国人的研究中检查冠状动脉疾病和抑郁症之间的关系，重点是了解遗传因素如何与抑郁症症状相互作用，从而对冠状动脉疾病产生如此强烈的负面影响。