Genetics Determinants of Extreme Phenotypes of Subclinical Atherosclerosis

应聘者描述(由申请者提供)：应聘者在面向患者的研究(POR)中提出了一个多方面的指导、职业发展和研究计划，目的是为了未来预防中风而对不明原因的亚临床颈动脉粥样硬化表型的遗传决定因素进行研究。该计划将建立在候选人在颈动脉超声成像标志物评估、流行病学和当前基因项目方面的既定优势基础上。这项建议将为初级受训人员提供获得POR培训的机会。K24奖项将允许有保护的时间，以便候选人可以将90%的专业努力投入到指导和开发针对住院医生和研究员(神经病学住院医生和临床研究员计划)和其他受训人员的正式指导计划，以及用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)帮助受训者发展他们的研究项目；(4)一对一的指导。这一K24奖项将包括为候选人提供专业和研究职业发展，以获得遗传流行病学方面的新知识和技能。正在进行的候选基因和亚临床颈动脉粥样硬化的POR将作为拟议研究的主要目标的背景，以(1)通过在根据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产生残余分数来识别患有不明原因的亚临床动脉粥样硬化(USA)和不明原因的抗动脉粥样硬化(UPA)的个体；(2)通过进行全基因组关联研究来识别与USA和uPA相关的等位基因；以及(3)评估颈动脉斑块负担的3年变化，并在uPA和USA的样本中识别与这种变化相关的等位基因。这一K24奖项将有助于实现候选人在以下方面的长期目标：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，以增加能够在神经学领域开展现代而严格的POR的内科科学家的数量。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)的新的遗传决定因素，并指导年轻的受训者进行研究。寻找中风先兆的遗传标记，将有助于通过基因筛查及早识别中风高危人群。这些发现将改善中风的预防，这对公共卫生非常重要。

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.