Integrating genomic and nongenomic risk for coronary artery disease

整合冠状动脉疾病的基因组和非基因组风险

• 批准号: 10524541
• 负责人: Akl C Fahed
• 金额: $ 16.89万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-10 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10524541
• 关键词: Active Learning; Address; Adherence; Adoption; Advisory Committees; African; Age; All of Us Research Program; Asian ancestry; Attenuated; Birth; Blood Circulation; Blood Glucose; Blood Pressure; Cardiology; Cardiovascular system; Caregivers; Cause of Death; Cholesterol; Clinical; Clinical Data; Complement; Complex; Computational Biology; Coronary Arteriosclerosis; Data; Data Set; Derivation procedure; Diet; East Asian; Environment; Environmental Exposure; European; Exercise; Familial Hypercholesterolemia; Fibrinogen; Foundations; Funding; Future; General Hospitals; Genes; Genetic; Genetic Diseases; Genetic Risk; Genome; Genomic medicine; Genomics; Genotype; Grant; Hand; Hematopoiesis; Hematopoietic stem cells; Heritability; Hispanic ancestry; Human Genetics; Individual; Inherited; Institutes; Internal Medicine; International; Intervention; K-Series Research Career Programs; Knowledge; Life; Life Style; Massachusetts; Medicine; Mentors; Mentorship; Methods; Modeling; Morbidity - disease rate; Myocardial Infarction; Paper; Participant; Performance; Persons; Pharmacology; Phase; Physicians; Play; Population; Positioning Attribute; Predictive Analytics; Prevention; Probability; Process; Productivity; Prospective cohort study; Publishing; Race; Research; Research Personnel; Risk; Risk Factors; Role; Scientist; Smoking; Somatic Mutation; South Asian; Subgroup; System; Testing; Time; Training; Training Activity; United States National Institutes of Health; Validation; Variant; Weight; Work; Writing; age related; base; biobank; cardiovascular risk factor; career; clinical practice; clinical risk; cloud based; data access; disorder risk; experience; genomic variation; healthy lifestyle; improved; individual variation; instructor; lifestyle data; medical schools; mortality; multi-ethnic; multidisciplinary; non-genomic; portability; predictive modeling; responsible research conduct; risk prediction; risk stratification; skills; staff intervention; treatment risk

PROJECT SUMMARY Candidate. Akl Fahed, MD, MPH is a board-certified physician in internal medicine, cardiology, and interventional cardiology on staff at the Massachusetts General Hospital (MGH). He is also instructor in medicine at Harvard Medical School (HMS) and postdoctoral scholar at the Broad Institute of Harvard/MIT. He has a track record of scientific commitment and productivity at each phase of training and has published 26 papers – including 18 as first author – in cardiovascular genetics over the past decade. He now seeks to expand upon previous training in cardiology and human genetics to catalyze a career focused on improving prevention and treatment of coronary artery disease. Mentorship, Training Activities, and Environment. Dr. Fahed will perform the proposed work at MGH and the Broad under the mentorship of Dr. Patrick Ellinor, a physician-scientist and international leader in cardiovascular genetics with an outstanding track record for mentorship and Dr. Pradeep Natarajan, a physician-scientist with expertise in coronary artery disease genetics and prevention. This mentorship team will be complemented by a highly committed and accomplished Advisory Committee of Drs. Peter Kraft and Heidi Rehm. Formal coursework will enhance a multi-disciplinary experiential learning effort to gain requisite skills in computational biology, predictive analytics, and responsible research conduct. Research. Coronary artery disease (CAD) remains a leading cause of death worldwide despite improved treatment of risk factors. Genomic risk provides opportunity for earlier recognition and targeted intervention prior to onset of risk factors, but there are two key barriers for its use: 1) There is no single model that combines genomic and nongenomic factors to predict absolute risk of CAD, and 2) existing genomic risk prediction underperforms in non-European ancestries. To address these knowledge gaps, the PI will first develop and validate a genomic risk model for CAD that combines monogenic, polygenic, and somatic variation using data on >460,000 European ancestry individuals. Second, he will develop and validate an integrated risk model for CAD that combines genomic and nongenomic (blood pressure, cholesterol, blood sugar, exercise, weight, diet, and smoking) risk drivers in European ancestry individuals. Third, he will optimize this model for individuals of African, South Asian, East Asian and Hispanic ancestries using data on >150,000 individuals from several multiethnic studies. Successful completion of the proposed studies will lay the scientific foundation for disclosing integrated risk information for CAD to individuals and their caregivers to facilitate targeted interventions. Furthermore, the proposal will provide key training of the PI to facilitate his transition to an independent physician investigator in cardiovascular genetics and the data generated will serve as the basis for a future R01 application.

项目摘要 候选人Akl Fahed，医学博士，公共卫生硕士是内科，心脏病学和 马萨诸塞州总医院（MGH）的介入心脏病学工作人员。他也是讲师， 他是哈佛医学院（HMS）的医学博士和哈佛/麻省理工学院布罗德研究所的博士后学者。他 在每个培训阶段都有科学承诺和生产力的跟踪记录，并已发表了26篇 在过去的十年中，他发表了18篇心血管遗传学论文，其中包括18篇第一作者。他现在寻求 扩展以前在心脏病学和人类遗传学的培训，以促进职业生涯的重点是改善 冠心病的预防和治疗。指导，培训活动和环境。博士 Fahed将在MGH和Broad进行拟议的工作，并在帕特里克埃林诺博士的指导下进行。 内科医生兼科学家，心血管遗传学领域的国际领导者， 导师和Pradeep Natarajan博士，一位在冠状动脉疾病遗传学方面具有专业知识的医生-科学家 和预防这个指导团队将由一个高度承诺和成就的顾问补充， 彼得·克拉夫特博士和海蒂·雷姆博士委员会。正式的课程将提高多学科 体验式学习努力获得计算生物学，预测分析和负责任的必要技能 研究行为。Research.冠状动脉疾病（CAD）仍然是全球死亡的主要原因 尽管对危险因素的治疗有所改善。基因组风险提供了早期识别和 在危险因素出现之前进行有针对性的干预，但其用途：1）没有 结合基因组和非基因组因素预测CAD绝对风险的单一模型，以及2）现有 基因组风险预测在非欧洲血统中表现不佳。为了弥补这些知识差距，PI 将首先开发和验证CAD的基因组风险模型，该模型结合了单基因、多基因和体细胞 使用超过460，000个欧洲血统个体的数据进行变异。其次，他将制定和验证一个 结合基因组和非基因组（血压、胆固醇、血液 糖，运动，体重，饮食和吸烟）的风险驱动因素在欧洲血统的个人。第三，他会优化 该模型适用于非洲人、南亚人、东亚人和西班牙裔人，使用的数据超过150，000 几个多民族研究的人。若能顺利完成拟议的研究， 向个人及其护理人员披露CAD综合风险信息的科学基础， 促进有针对性的干预。此外，建议亦会为首席研究员提供主要培训， 过渡到心血管遗传学的独立医生研究者，产生的数据将用于 作为未来R 01应用的基础。