GENETIC AND NON-GENETIC RISK FACTORS FOR ROTATOR CUFF DISEASE

项目概要/摘要：与母公司赠款相比没有变化 退行性肩袖疾病是最常见的原因，肩关节残疾， 导致比身体其他部位更高的平均休假天数。肩袖手术率也 增加，给医疗保健系统带来沉重负担。鉴于高成本和发病率， 有症状的肩袖疾病，重要的是要准确识别高风险亚组， 预防工作。这需要了解重要的风险因素，并建立和验证 在大型前瞻性研究中的预测模型。Yanik博士的首要职业目标是发现新的见解 研究肩袖疾病的病因和进展，可以直接告知临床决策， 预防方法。在目前的研究中，她假设遗传和职业因素 显著促进症状性肩袖疾病的发展，并且这些因素 结合已知的风险因素可以准确预测未来的疾病风险。具体来说，亚尼克博士提议 研究的目的是：1）确定遗传标记与有症状的肩袖疾病风险的关联， 2)阐明职业上肢需求与 症状性肩袖疾病风险，以及3）开发症状性肩袖疾病的预测模型 风险包括遗传和非遗传风险因素。为了实现这些目标，Yanik博士将利用英国 生物银行，一个大型的前瞻性，基于人群的队列，有500,182人的广泛数据， 人口统计学、行为、职业、医院诊断（包括> 3，500例有症状的肩袖疾病 诊断），以及> 800，000个遗传标记的完整基因型信息。Yanik博士是唯一有资格 从事这一研究，因为她在流行病学方法方面受过广泛的训练， 使用各种数据资源来解决独特的研究问题。然而，成功的执行 为确保这项研究的有效开展和今后研究的有效规划，需要在以下领域开展更多培训： 1)肩袖疾病的病理生物学和临床护理，2）统计遗传学和遗传流行病学，3） 职业卫生和职业暴露评估; 4）花岗岩专业技能， 流行病学、研究交流和领导力。Yanik博士的指导团队由Jay Keener博士领导， 她非常致力于成为一名成功的独立调查员。她的研究方向 一些潜在的影响。肩袖疾病重要遗传标记的发现将 允许更集中地观察具有更详细临床特征的队列中遗传易感性的具体指标， 信息，而确定职业风险可能导致确定可改变的风险行为。 最后，结合这些风险因素的预测模型可以适用于帮助识别高风险个体。 在各种情况下的眼泪的风险，可以帮助预防工作和临床决策。

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