Genetics Determinants of Extreme Phenotypes of Subclinical Atherosclerosis

描述（由申请人提供）：候选人提出了一个面向患者的研究（POR）的多方面指导，职业发展和研究计划，研究亚临床颈动脉粥样硬化不明原因表型的遗传决定因素，目标是未来预防中风。该计划将建立在候选人在评估颈动脉超声成像标记物，流行病学和当前遗传项目方面的既定优势之上。这一建议将为初级受训人员提供机会，使他们能够在贫困地区接受培训。K24奖将允许受保护的时间，以便候选人可以将其90%的专业精力用于指导和开发正式的指导计划，为住院医生和研究员（神经病学住院医生和临床研究员计划）和其他学员，以及她在遗传流行病学方面的研究和职业发展。指导计划将包括(1)研究方法论、流行病学、分析方法、遗传学和科学写作的教学讲座；（二）组织研究会议、研讨会、会议；(3)帮助学员开展研究项目；(4)一对一辅导。该K24奖将为候选人提供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。关于候选基因和亚临床颈动脉粥样硬化的候选持续POR将作为拟议研究的主要目的的背景：(1)通过在传统血管危险因素拟合的亚临床颈动脉表型多变量回归模型中产生残差评分，识别患有不明原因亚临床动脉粥样硬化（USA）和不明原因动脉粥样硬化保护（UPA）的个体；(2)通过全基因组关联研究确定与USA和UPA相关的等位基因；(3)在UPA和美国的样本中评估颈动脉斑块负荷的3年变化，并确定与此变化相关的等位基因。K24奖将有助于实现候选人的长期目标，提高POR，建立正式的POR指导计划，为受训者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的内科科学家的数量。1

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.