The Genetics of Hand Osteoarthritis Study (GHOST)

简介(申请人提供)：石森真理子博士致力于临床研究的学术生涯。她在风湿病方面拥有深厚的临床背景，并在临床研究方面拥有新兴的专业知识。她现在寻求提高自己在设计和实施未来研究方面的技能，并获得培训、经验和支持，使她能够进行独立的、由研究人员发起的临床研究。她组建了一支杰出的导师和合作者团队，其中包括CSMC医学遗传科主任Jerome Rotter医学博士，他的主要研究兴趣是常见疾病的遗传流行病学；Daniel Cohn Ph.D.，高级分子遗传学家，CSMC国际骨骼发育不良登记的联席主任；Michael Weisman，医学博士，CSMC风湿科主任，负责维护CSMC的研究对象登记，并已成功招募患者参加NIH资助的RA、OA、SLE和AS的重大结果研究。这三位导师总共有近75年的培训和指导住院医生以及博士后学者走向学术生涯的经验和成功。K23奖项的目标是1)进一步发展她在生物统计学、遗传学、流行病学以及研究设计和方法方面的技能；2)使她能够将风湿学临床研究与基因研究相结合；3)从共同导师和顾问那里获得指导，以促进她的职业发展。她的具体目标是：1)招募400名手部骨关节炎(OA)先证者，通过使用特定的、预先确定的临床和放射学标准，对疾病进行仔细的表型鉴定；2)通过分析受手部骨关节炎及其兄弟姐妹影响的研究对象，确定手部OA和特定表型的熟悉度和遗传性；3)利用全基因组关联方法，确定手部OA的一般遗传位点以及不同的、特定的、临床和放射学表型。这项研究的发现将提供与手部骨性关节炎相关的遗传机制的新信息，并可能有助于我们理解这种导致许多人残疾和生活质量下降的疾病的发病机制、治疗和可能的预防。

DESCRIPTION (provided by applicant): Dr. Mariko Ishimori is strongly committed to pursuing an academic career in clinical research. She possesses a strong clinical background in rheumatology and an emerging expertise in clinical research. She now seeks to enhance her skills in the design and implementation of future studies and gain the training, experience, and support that will allow her to perform independent, investigator-initiated clinical research. She has assembled an outstanding team of mentors and collaborators including Jerome Rotter, M.D., the Director of the Division of Medical Genetics at CSMC whose major research interest is in the genetic epidemiology of common diseases; Daniel Cohn Ph.D., a senior molecular geneticist who co-directs the International Skeletal Dysplasia Registry at CSMC, and Michael Weisman, M.D., Director of the Division of Rheumatology at CSMC who is responsible for maintaining the CSMC registry of research subjects and has successfully recruited patients for major NIH-funded outcome studies in RA, OA, SLE, and AS. Together these three mentors have almost 75 years of combined experience and success in training and mentoring residents, and post-doctoral fellows towards academic careers. The K23 award objectives are to 1) further develop her skills in biostatistics, genetics, epidemiology, and research design and methodology; 2) enable her to integrate rheumatology clinical research with genetic studies; and 3) obtain guidance from co-mentors and advisors to facilitate her career development. Her specific aims are to 1) recruit a cohort of 400 probands with hand osteoarthritis (OA) and conduct careful phenotyping of disease through the use of specific, predetermined clinical and radiographic criteria; 2) determine the familiality and heritability of hand OA and specific phenotypes by analyzing study subjects affected by hand OA and their siblings; 3) identify genetic loci for hand OA in general and for different, specific, clinical and radiographic phenotypes using genome-wide association methods. Findings from this study will provide new information on the genetic mechanisms associated with hand OA and may aid our understanding of disease pathogenesis, treatment, and possibly prevention for a condition that causes disability and diminished quality of life in many people.