Genetics Determinants of Extreme Phenotypes of Subclinical Atherosclerosis

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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.