Precision Cardiovascular Medicine for Multi-Ethnic Populations

为多民族人群提供精准心血管医学

• 批准号: 10582991
• 负责人: ARJUN KUMAR MANRAI
• 金额: $ 15.54万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-07 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10582991
• 关键词: Africa; African American population; Age; American; Arrhythmogenic Right Ventricular Dysplasia; Award; Bioinformatics; Boston; Cardiac; Cardiology; Cardiovascular Diseases; Cardiovascular system; Caring; Catalogs; Clinic; Clinical; Clinical Research; Collaborations; Confusion; Data; Data Set; Databases; Decision Making; Defibrillators; Development; Dilated Cardiomyopathy; Echocardiography; Enrollment; Ensure; Ethnic Origin; Ethnic group; Europe; European; Family; Gender; General Population; Genetic; Genetic Risk; Genetic Variation; Genome; Genomics; Goals; Healthcare Systems; Heart Diseases; Hospitals; Hypertrophic Cardiomyopathy; Implant; Improve Access; Individual; Inherited; International; K-Series Research Career Programs; Laboratories; Lead; Left Ventricular Hypertrophy; Longitudinal Studies; Measurement; Measures; Medicine; Mentors; Minority Women; Molecular; Molecular Abnormality; Morphology; National Heart, Lung, and Blood Institute; Normal Range; Pathogenicity; Pathologic; Patients; Phenotype; Physicians; Play; Population; Population Heterogeneity; Positioning Attribute; Practice Guidelines; Prevalence; Quantitative Genetics; Recording of previous events; Reduce health disparities; Reference Values; Research; Research Personnel; Research Proposals; Research Training; Risk; Societies; Technology; Test Result; Testing; Training; Translating; Translational Research; United States; Validation; Variant; Ventricular Remodeling; Work; biomedical data science; biomedical informatics; burden of illness; cardiac muscle disease; career development; clinical practice; comorbidity; cost; disorder risk; ethnic difference; ethnic minority; ethnic minority population; evidence base; exome; falls; genetic testing; genetic variant; health care disparity; health disparity; heterogenous data; high dimensionality; improved; inherited cardiomyopathy; insurance claims; meetings; multi-ethnic; novel; population health; precision medicine; prevent; risk variant; sudden cardiac death

PROJECT SUMMARY/ABSTRACT This award will support mentored training and research needed for Dr. Arjun K. Manrai to transition to an independent investigator position bridging biomedical informatics, cardiovascular medicine, and population health. Throughout this award, Dr. Manrai will be mentored by Drs. Isaac S. Kohane, Joseph Loscalzo, and John P.A. Ioannidis. The long-term goal of Dr. Manrai's research is to improve cardiovascular care and reduce health disparities in multi-ethnic populations. A necessary step towards this goal is to clarify the impact of the ethnicity gap between past studies and current clinical practice. Dr. Manrai's K01 proposed research builds directly off of his previous work in translating clinical genomics across multi-ethnic populations, and includes large-scale analyses of diverse populations (N > 45,000,000) to investigate the appropriateness of existing genetic and clinical criteria for defining pathologic left ventricular hypertrophy (LVH) across different ethnic groups. Dr. Manrai will use heterogeneous datasets (genomic, clinical, and insurance claims data spanning tens of millions of individuals) to clarify the range of normal—and the appropriateness and impact of extant criteria for defining abnormal—molecular and clinical variation in diverse populations. This work will enable Dr. Manrai to: (1) characterize disease risks for genotype variation associated with the inherited heart disease hypertrophic cardiomyopathy (HCM) across ancestrally diverse populations; (2) develop ethnicity-specific phenotype reference ranges for cardiac morphology measures; and (3) measure the related healthcare systems impact using large-scale insurance claims data. In addition to the proposed research, Dr. Manrai will use this award to extend his background in biomedical data science and clinical genomics with extensive, hands-on clinical cardiology training and career development activities. Specifically, Dr. Manrai will: (1) enroll in formal echocardiography training courses and obtain clinical cardiology exposure; (2) attend leading cardiology meetings; (3) obtain training in health disparities and translational research; and (4) increase professional development. As part of his K01 career development activities, Dr. Manrai will work extensively in cardiology clinics around Boston and explore international clinical and research collaborations with clinics in Europe and Africa. This career development award is expected to enable Dr. Manrai to transition to an independent investigator position and lead directly to an R01 research proposal applying the research and training acquired during the award period to study a broader set of diseases of the heart muscle (inherited cardiomyopathies including dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy). Dr. Manrai's K01 proposed research is expected to yield the largest existing catalogue of multi-ethnic cardiac morphology and genetic variation related to LVH. This information will assist physicians, researchers, and patients making decisions with these data daily.

项目总结/摘要 该奖项将支持Arjun K博士所需的指导培训和研究。Manrai过渡到一个 一个独立研究者的职位，负责连接生物医学信息学、心血管医学和人口学 健康在整个奖项，曼莱博士将由艾萨克博士指导。Kohane，Joseph Loscalzo， John P.A.约翰Manrai博士研究的长期目标是改善心血管护理， 多民族人口的健康差距。实现这一目标的一个必要步骤是澄清 过去研究和当前临床实践之间的种族差距。Manrai博士提出的K 01研究建立 直接从他以前的工作中翻译临床基因组学跨多种族人群，包括 对不同人群（N > 45，000，000）进行大规模分析，以调查现有 在不同种族中定义病理性左心室肥大（LVH）的遗传和临床标准 组Manrai博士将使用异构数据集（基因组、临床和保险索赔数据， 数千万人），以澄清正常的范围，以及现有的适当性和影响， 在不同人群中定义异常分子和临床变异的标准。这项工作将使博士。 Manrai：（1）描述与遗传性心脏病相关的基因型变异的疾病风险 肥厚型心肌病（HCM）在祖先不同的人群;（2）发展种族特异性 用于心脏形态测量的表型参考范围;以及（3）测量相关的医疗保健 系统使用大规模保险索赔数据的影响。 除了拟议的研究，Manrai博士将利用这一奖项，以扩大他的背景， 生物医学数据科学和临床基因组学，具有广泛的动手临床心脏病学培训和职业生涯 发展活动。具体而言，Manrai博士将：（1）参加正式的超声心动图培训课程， 获得临床心脏病学知识;（2）参加领先的心脏病学会议;（3）获得健康培训 差异和翻译研究;（4）增加专业发展。作为K 01职业生涯的一部分， 开发活动，Manrai博士将在波士顿周围的心脏病诊所广泛工作，并探索 与欧洲和非洲的诊所开展国际临床和研究合作。 这一职业发展奖预计将使Manrai博士过渡到一个独立的 研究者定位并直接导致R 01研究提案，应用所获得的研究和培训 在获奖期间，研究更广泛的心肌疾病（遗传性心肌病 包括扩张型心肌病和致血栓性右心室心肌病）。万来博士的K 01 拟议的研究预计将产生现有最大的多种族心脏形态目录， 与LVH相关的遗传变异。这些信息将有助于医生，研究人员和患者 这些数据每天。

项目成果

Potential Excessive Testing at Scale: Biomarkers, Genomics, and Machine Learning.

• DOI: 10.1001/jama.2019.0286
• 发表时间: 2019-02-26
• 期刊: JAMA
• 作者: Mandl KD;Manrai AK
• 通讯作者: Manrai AK

In Search of a Better Equation - Performance and Equity in Estimates of Kidney Function.

• DOI: 10.1056/nejmp2028243
• 发表时间: 2021-02-04
• 期刊: The New England journal of medicine
• 作者: Diao JA;Inker LA;Levey AS;Tighiouart H;Powe NR;Manrai AK
• 通讯作者: Manrai AK

Positive Predictive Value of the Thumb-Palm Test for General Population Screening of Ascending Aortic Aneurysm.

拇指手掌试验对一般人群升主动脉瘤筛查的阳性预测价值。

• DOI: 10.1016/j.amjcard.2021.08.029
• 发表时间: 2021
• 期刊: The American journal of cardiology
• 作者: Diao,JamesA;Wu,GloriaJ;Manrai,ArjunK
• 通讯作者: Manrai,ArjunK

Association of 152 Biomarker Reference Intervals with All-Cause Mortality in Participants of a General United States Survey from 1999 to 2010.

• DOI: 10.1093/clinchem/hvaa271
• 发表时间: 2021-03-01
• 期刊: Clinical chemistry
• 影响因子: 9.3
• 作者: Pho N;Manrai AK;Leppert JT;Chertow GM;Ioannidis JPA;Patel CJ
• 通讯作者: Patel CJ

What about the environment? Leveraging multi-omic datasets to characterize the environment's role in human health.

环境怎么样？

• 发表时间: 2021
• 期刊: Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing
• 作者: Passero,Kristin;Setia-Verma,Shefali;McAllister,Kimberly;Manrai,Arjun;Patel,Chirag;Hall,Molly
• 通讯作者: Hall,Molly