2 Degenerative rotator cuff disease is the most frequent cause of shoulder disability, and injuries of the shoulder 3 lead to higher median days away from work than any other body part. Rotator cuff surgery rates are also 4 increasing, leading to significant burdens on the healthcare system. Given the high costs and morbidity of 5 symptomatic rotator cuff disease, it will be important to identify high-risk subgroups accurately to enable 6 prevention efforts. This requires knowledge of important risk factors as well as the creation and validation of 7 predictive models in large, prospective studies. Dr. Yanik?s overarching career goal is to discover new insights 8 into the etiology and progression of rotator cuff disease that can directly inform clinical decision-making and 9 prevention approaches. For the present study, she hypothesizes that genetic and occupational factors 10 contribute significantly to the development of symptomatic rotator cuff disease, and that these factors 11 combined with known risk factors can accurately predict future disease risk. Specifically, Dr. Yanik?s proposed 12 research aims are to: 1) determine associations of genetic markers with symptomatic rotator cuff disease risk, 13 2) elucidate the magnitude of the association between occupational upper extremity demands and 14 symptomatic rotator cuff disease risk, and 3) develop a prediction model for symptomatic rotator cuff disease 15 risk including genetic and non-genetic risk factors. To accomplish these aims, Dr. Yanik will use the UK 16 Biobank, a large prospective, population-based cohort of 500,182 people with extensive data on 17 demographics, behaviors, occupations, hospital diagnoses (including >3,500 symptomatic rotator cuff disease 18 diagnoses), and complete genotype information for >800,000 genetic markers. Dr. Yanik is uniquely qualified 19 to pursue this line of research, as she has extensive training in epidemiologic methods and has experience 20 using a diverse array of data resources to address unique research questions. However, successful execution 21 of this research and effective planning for future research will require additional training in the following areas: 22 1) the pathobiology and clinical care of rotator cuff disease, 2) statistical genetics and genetic epidemiology, 3) 23 occupational health and occupational exposure assessment, and 4) professional skills in grantsmanship, 24 epidemiology, research communication, and leadership. Dr. Yanik?s mentoring team, led by Dr. Jay Keener, is 25 highly committed to her development as a successful independent investigator. Her line of research has a 26 number of potential implications. The discovery of important genetic markers for rotator cuff disease would 27 allow a more focused look at specific measures of genetic susceptibility in cohorts with more detailed clinical 28 information, while determining occupational risks could lead to the identification of modifiable risk behaviors. 29 Finally, prediction models incorporating these risk factors can be adapted to help identify individuals at high- 30 risk for tears in various settings and could aid both prevention efforts and clinical decision-making.
/Pubic Health Relevance Statement: Rotator cuff disease is the most frequent cause of shoulder disability, leading to substantial morbidity and economic costs. As a part of my long-term goal to develop a rotator cuff disease epidemiology research program, this proposal aims to identify genetic and occupational factors that contribute to symptomatic rotator cuff disease risk and to develop a prediction model for incident symptomatic rotator cuff disease based on known and newly discovered risk factors. Determining important underlying risk factors for symptomatic rotator cuff disease can enable prevention efforts, while developing accurate prediction models can support the identification of high-risk groups for targeted interventions.