Gender Differences in Outcomes and Genetic Associations of Rheumatoid Arthritis

描述（由申请人提供）：该提案是通过指导研究科学家发展奖（K01）计划的机制，为NIAMS职业发展奖提供5年的资金。培训奖的目标是发展候选人在流行病学方法，数据分析和解释方面的知识和技能，并在疾病表现，治疗和治疗结果方面为她提供对临床流变学的扎实理解，以补充她已经在类风湿关节炎（RA）遗传学方面积累的专业知识，使她能够独立进行遗传流行病学研究。职业发展计划将培养候选人在以下方面的技能：1）流行病学方法和应用于复杂疾病研究，2）临床流变学，以及3）流行病学方法在基因关联研究背景下对遗传数据的应用。职业发展的方法包括1）拟议的研究，2）博士的指导。纳尔逊弗雷默，林赛克里斯韦尔和约恩奥尔森，3）咨询专家在临床流变学，并观察流变学诊所，4）正式的流行病学课程，导致硕士流行病学，5）参加科学会议，6）数据准备提交手稿的同行评审的期刊，并利用职业发展奖产生的初步数据准备R01补助金申请。该研究计划的主要目的是使用流行病学方法研究RA患者疾病特征，治疗反应以及与候选基因标记物的相关性的性别差异。这些目标将检验以下假设：男性类风湿关节炎患者，特别是那些发病年龄较小的患者，具有更高的疾病遗传和非遗传风险因素负荷，因此具有更严重的疾病表现和可能对治疗的不同反应。更好地了解RA的性别差异可能会提供有关潜在疾病机制的线索，也可能对RA的预后和治疗产生重要影响。凭借拟议的导师制，优秀的资源，研究环境和候选人的先前培训，K01奖将促进候选人过渡到成为风湿性疾病遗传学领域的独立研究人员。

DESCRIPTION (provided by applicant): This proposal is for 5 years of funding for a NIAMS Career Development Award, through the mechanism of the Mentored Research Scientist Development Award (K01) program. The goal of the training award is to develop the candidate's knowledge and skills in epidemiologic methods, data analysis and interpretation, as well as to provide her with a solid understanding of clinical rheumatology in terms of disease manifestations, treatment and treatment outcomes, to complement the expertise that she has already gathered in the genetics of rheumatoid arthritis (RA), leading to her transition to being able to independently conduct genetic epidemiology studies. The career development plan will develop the candidate's skills in 1) epidemiology methods and applications to complex disease research, 2) clinical rheumatology, and 3) application of epidemiology methods to genetic data within the context of gene association studies. Methods of career development include 1) the proposed study, 2) the mentorship of Drs. Nelson Freimer, Lindsey Criswell and Jorn Olsen, 3) consultation with experts in clinical rheumatology, and observation at rheumatology clinics, 4) formal coursework in epidemiology, leading to a Masters in Epidemiology, 5) attendance at scientific meetings, 6) data preparation for submission of manuscripts to peer-reviewed journals, and preparation of R01 grant application using preliminary data generated from this career development award. The main objective of the research plan is to examine gender differences in disease features, responses to treatment, and associations with candidate gene markers among RA patients, using epidemiological methods. These aims will test the hypothesis that male RA patients, in particular those with younger age at onset, have a higher load of genetic and non-genetic risk factors for the disease, and hence have more severe disease manifestations and possibly different responses to treatment. A better understanding of the sex differences in RA might provide clues about underlying disease mechanisms and could also have an important impact on RA prognosis and therapy. With the proposed mentorship, outstanding resources, research environment and the candidate's prior training, a K01 award will facilitate the candidate's transition to becoming an independent researcher in the field of rheumatic disease genetics.