Genetics Determinants of Extreme Phenotypes of Subclinical Atherosclerosis

描述（由申请人提供）：候选人提出了一个多方面的指导，职业发展和研究计划，以患者为导向的研究（POR）的遗传决定因素的原因不明的表型的亚临床颈动脉粥样硬化与未来预防中风的目标。该计划将建立在候选人在颈动脉超声成像标记物，流行病学和当前遗传项目评估方面的优势之上。这项建议将为初级学员提供机会，接受有关职业康复训练。K24奖将允许受保护的时间，使候选人可以投入90%的专业努力，为居民和研究员（神经病学的居民和临床研究员计划）和其他受训人员提供指导和制定正式的导师计划，并致力于她在遗传流行病学方面的研究和职业发展。导师计划将包括（1）关于研究方法，流行病学，分析方法，遗传学和科学写作的教学讲座;（2）组织研究会议，研讨会和会议;（3）帮助学员开发他们的研究项目;和（4）一对一的指导。该K24奖项将包括候选人的专业和研究职业发展，以获得遗传流行病学的新知识和技能。候选基因和亚临床颈动脉粥样硬化的候选持续POR将作为所提出研究的主要目的的背景，以（1）通过在从传统血管风险因素拟合的亚临床颈动脉表型的多变量回归模型中生成残差评分来识别具有原因不明的亚临床动脉粥样硬化（USA）和原因不明的抗动脉粥样硬化（UPA）保护的个体;（2）通过进行全基因组关联研究鉴定与USA和UPA相关的等位基因;和（3）评估颈动脉斑块负荷的3年变化，并鉴定与UPA和USA样品中的这种变化相关的等位基因。这个K24奖项将有助于实现候选人的长期目标，提高POR，建立正式的POR导师计划，为学员提供执行独立研究想法的资源，并创造一个鼓舞人心的智力环境，以增加能够在神经病学中进行现代和严格的POR的医生科学家的数量。1 公共卫生相关性： 中风是导致死亡和残疾的主要原因。该项目旨在发现亚临床动脉粥样硬化（中风的前兆）的新遗传决定因素，并指导年轻学员进行研究。找到中风前兆的遗传标记将导致通过遗传筛查早期识别中风高危人群。这些发现将改善中风预防，这对公共卫生具有重要意义。

DESCRIPTION (provided by applicant): The candidate proposes a multifaceted mentoring, career development, and research plan in patient- oriented research (POR) on genetic determinants of unexplained phenotypes of subclinical carotid atherosclerosis with the goal of future prevention of stroke. This plan will build on the candidate's established strengths in assessment of carotid ultrasound imaging markers, epidemiology, and current genetic project. This proposal will provide opportunities for junior trainees to obtain training in POR. The K24 award will allow for protected time so that the candidate can devote 90% of her professional effort towards mentoring and developing a formal mentorship program for residents and fellows (The Resident and Fellow Clinician Researcher Program in Neurology) and other trainees, and towards her research and career development in genetic epidemiology. The mentorship program will include (1) Didactic lectures on research methodology, epidemiology, analytical methods, genetics, and scientific writing; (2) Organizing research meetings, seminars, and conferences; (3) Helping trainees to develop their research projects; and (4) One-on-one mentoring. This K24 award will include professional and research career development for the candidate to gain new knowledge and skills in genetic epidemiology. The candidate ongoing POR on the candidate genes and subclinical carotid atherosclerosis will serve as a background for the primary aims of the proposed research to (1) identify individuals with unexplained subclinical atherosclerosis (USA) and unexplained protection against atherosclerosis (UPA) by generating residual scores in the multivariable regression model of subclinical carotid phenotypes fitted from the traditional vascular risk factors; (2) identify alleles associated with USA and UPA by performing a genome wide association study; and (3) assess the 3- year change in carotid plaque burden and identify alleles associated with this change in the sample of UPA and USA. This K24 award will help achieving the candidate's long-term goals in enhancing POR, establishing formal POR mentorship program, providing resources to perform independent research ideas for trainees, and creating an inspiring intellectual environment needed to increase the number of physician-scientists capable of carrying out modern and rigorous POR in neurology. 1 PUBLIC HEALTH RELEVANCE: Stroke is a leading cause of death and disability. This project is designed to discover new genetic determinants of subclinical atherosclerosis, a precursor of stroke, and to mentor young trainees in research. Finding genetic markers for precursors of stroke would lead to early identification of persons at high risk for stroke through genetic screening. These findings would improve stroke prevention, which is of great public health importance.