The Genetics of Hand Osteoarthritis Study (GHOST)

描述（由申请人提供）：石森玛丽子博士坚定地致力于临床研究的学术生涯。她在风湿病学方面有很强的临床背景，在临床研究方面具有新兴的专业知识。她现在寻求提高她在未来研究的设计和实施方面的技能，并获得培训、经验和支持，使她能够独立地进行研究者发起的临床研究。她组建了一个杰出的导师和合作者团队，包括Jerome Rotter，医学博士，CSMC医学遗传学部主任，主要研究兴趣是常见病的遗传流行病学；Daniel Cohn博士是CSMC国际骨骼发育不良登记处的高级分子遗传学家，Michael Weisman博士是CSMC风湿病科主任，他负责维护CSMC研究对象的登记处，并成功招募了患者进行美国国立卫生研究院资助的RA， OA， SLE和AS的主要结果研究。这三位导师在培训和指导住院医生和博士后走向学术生涯方面拥有近75年的经验和成功经验。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、研究设计和方法方面的技能；2)使她能够将风湿病临床研究与遗传学研究相结合；3)获得共同导师和顾问的指导，促进其职业发展。她的具体目标是1)招募400名患有手骨关节炎（OA）的先证者，并通过使用特定的、预先确定的临床和放射学标准对疾病进行仔细的表型分析；2)通过分析患手性关节炎的研究对象及其兄弟姐妹，确定手性关节炎的熟悉性、遗传性和特异性表型；3)利用全基因组关联方法鉴定手部OA的一般遗传位点以及不同的、特定的、临床和放射学表型的遗传位点。这项研究的发现将提供与手部骨关节炎相关的遗传机制的新信息，并可能有助于我们了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.