Admixture Mapping of Coronary Heart Disease and Associated Metabolomic Markers in African Americans

非裔美国人冠心病和相关代谢组标记物的混合图谱

• 批准号: 10571022
• 负责人: Daniel Cruz
• 金额: $ 16.06万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-15 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10571022
• 关键词: Address; Admixture; African; African American; African American population; African ancestry; Alleles; Amino Acids; Biological; Biomedical Research; Cardiology; Cardiovascular Diseases; Cardiovascular system; Caring; Chronic Disease; Clinical; Communities; Complex; Coronary heart disease; Data; Diabetes Mellitus; Discrimination; Disease; Etiology; European; European ancestry; Exhibits; Foundations; Future; Gene Frequency; Genes; Genetic; Genetic Drift; Genetic Variation; Genome; Genomic Segment; Genomics; Goals; Health; High Density Lipoproteins; Hyperlipidemia; Hypertension; Individual; Institution; Israel; Jackson Heart Study; Laboratories; Low-Density Lipoproteins; Maps; Measures; Medical; Medical center; Methods; Minority Groups; Multi-Ethnic Study of Atherosclerosis; Obesity; Outcome; Participant; Pathogenesis; Pathway interactions; Patients; Pattern; Persons; Plasma; Population; Predictive Value; Preventive; Probability; Publishing; Quantitative Trait Loci; Research; Resources; Risk; Risk Assessment; Risk Factors; Risk Marker; Sampling; Signal Transduction; Societies; Socioeconomic Factors; Structure; Techniques; Technology; Testing; Training; Triglycerides; Underserved Population; United States; Variant; Work; admixture mapping; cardiometabolic risk; cardiometabolism; causal variant; circulating biomarkers; clinical risk; cohort; dietary; disease phenotype; experience; follow-up; genetic analysis; genetic association; genetic makeup; genetic selection; genetic variant; genome wide association study; genome-wide analysis; geographic difference; heart disease risk; high risk; improved; interest; liquid chromatography mass spectrometry; medical schools; member; metabolomics; multi-ethnic; multidisciplinary; multiple omics; novel; personalized care; precision medicine; psychosocial; trait; whole genome

Dr. Cruz is a practicing cardiologist with an interest in investigating the genetic underpinnings of circulating biomarkers and their association with health and disease. Dr. Cruz’s research interests primarily focus on historically understudied groups and understanding how varied genetic ancestry plays a role in disease pathogenesis. African Americans suffer disproportionately from many chronic diseases and in particular cardiovascular disease. African Americans have also not been included in many cardiovascular studies, raising the possibility that some results may not be applicable to them. Compounding these issues is the fact that traditional genetic analyses are not designed to account for the relatively complex genetic makeup that African Americans have, due to their African ancestry and admixture with other populations. This project aims to identify the circulating metabolites that are associated with coronary heart disease, investigate the portions of the genome that are of African continental origin, and use this correlation to identify specific genes that are associated both with African ancestry and coronary heart disease. Through intensive laboratory and didactic training in metabolomics and genetics, Dr. Cruz will harness the resources of Beth Israel Deaconess Medical Center, Harvard Medical School, and associated institutions to examine a disease of significant societal impact. Situated in a multi-disciplinary laboratory, Dr. Cruz will take advantage of novel metabolomic technologies and novel genetic analytical strategies to better decipher how genetic ancestry influences levels of circulating metabolites. He will use admixture mapping techniques, which take into account the heterogeneous genomic make up of African Americans, to better understand how the unique genomic structure of recently admixed populations may influence baseline circulating levels of metabolites. Using plasma samples from African American participants of the Jackson Heart Study and Multi-Ethnic Study of Atherosclerosis, metabolomics will be used to measure levels of circulating metabolites and assess which metabolites are associated with incident coronary heart disease, with over 15 years of follow up. Clinical traits associated with coronary heart disease like, diabetes, hypertension, obesity, and hyperlipidemia will also be analyzed. Using admixture mapping, regions of potential association between the metabolites of interest and African ancestry in the genome will be identified, allowing for higher power in identifying specific associated variants in those regions. As precision medicine offers the promise of more personalized care, it is incumbent on the biomedical research community to take into account the unique genetic makeup of all members of society. This project aims to offer specific pathophysiologic information for a historically understudied group of people. Ultimately Dr. Cruz intends on using his research efforts to provide better medical care to understudied and underserved populations, and in turn improve the health of society as a whole.

Cruz博士是一位执业心脏病专家，对研究循环系统疾病的遗传基础感兴趣。 生物标志物及其与健康和疾病的关系。克鲁兹博士的研究兴趣主要集中在 历史上研究不足的群体，了解不同的遗传祖先如何在疾病中发挥作用 发病机制非裔美国人患许多慢性病的比例不成比例， 心血管疾病非洲裔美国人也没有被纳入许多心血管研究， 有些结果可能不适用于他们。使这些问题更加复杂的是， 传统的遗传分析并没有考虑到非洲人相对复杂的遗传组成， 美国人，由于他们的非洲血统和与其他人口的混合。该项目旨在 确定与冠心病相关的循环代谢物，研究 非洲大陆起源的基因组，并使用这种相关性来识别特定的基因， 与非洲血统和冠心病都有关。通过密集的实验室和教学 在代谢组学和遗传学的培训，克鲁兹博士将利用贝丝以色列女执事医疗资源 中心，哈佛医学院，和相关机构，以检查一种疾病的重大社会 冲击位于多学科实验室，克鲁兹博士将利用新的代谢组学 技术和新的遗传分析策略，以更好地破译遗传祖先如何影响水平 循环代谢物。他将使用混合映射技术，该技术考虑了 异质基因组组成的非裔美国人，以更好地了解如何独特的基因组 最近混合人群的结构可能影响代谢物的基线循环水平。使用 来自杰克逊心脏研究和多种族研究的非裔美国人参与者的血浆样本， 代谢组学将用于测量循环代谢物的水平，并评估 代谢物与冠心病事件相关，随访超过15年。临床特点 糖尿病、高血压、肥胖症、高脂血症等冠心病相关疾病， 分析了使用混合物映射，感兴趣的代谢物之间的潜在关联区域， 基因组中的非洲血统将被识别，从而在识别特定相关基因方面具有更高的能力。 这些地区的变种。由于精准医疗提供了更多个性化护理的承诺， 生物医学研究界考虑到所有成员的独特基因组成， 社会该项目旨在为一组历史上未充分研究的 人最终，克鲁兹博士打算利用他的研究成果为未成年人提供更好的医疗服务。 和服务不足的人群，从而改善整个社会的健康状况。