HEREDITY IN OSTEOARTHRITIS--FARMINGTON OFFSPRING

骨关节炎的遗传——法明顿后代

• 批准号: 3791934
• 负责人: DAVID T FELSON
• 金额: --
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3791934
• 关键词: disease /disorder proneness /risk; family genetics; gene expression; genetic models; human subject; linkage mapping; longitudinal human study; osteoarthritis

In recent years, a substantial genetic component has been recognized for many common rheumatic diseases, including ankylosing spondylitis, rheumatoid arthritis and gout. Several families with severe and progressive osteoarthritis at an early age and with associated genetic abnormalities have been found suggesting that osteoarthritis may also be due to inherited abnormalities. Nonetheless, these families are unusual and it is unclear whether osteoarthritis in the population at large is frequently due to genetic abnormalities and, if so, what the pattern of genetic inheritance is. In fact, there is astonishingly little information about the genetics of osteoarthritis in populations. No epidemiologic studies of the heritability of osteoarthritis have ever been performed in North America. The objective of this project is to examine the heritable nature of generalized osteoarthritis by looking at the association of generalized disease in the Framingham cohort and their offspring in the Framingham offspring group. To accomplish this objective, we will study OA of the hands and knees in members of the Framingham offspring group who had both parents in the cohort previously assessed for OA. In order to accomplish these objectives, we will pursue several specific aims: 1) we will characterize generalized OA and known risk factors for it in the targeted offspring; 2) we will read previously obtained hand x-rays from targeted cohort subjects for OA and characterize generalized OA in cohort subjects; 3) using complex segregation analysis and adjusting for the likelihood of osteoarthritis by taking into account age, sex, and other risk factors, we will evaluate whether generalized OA segregates in families and assess whether the pattern of inheritance best fits a single major gene model (dominant, codominant, recessive), a multifactorial model, a mixed model (a single gene effect in multifactorial background) or does not aggregate in families; and 4) we will identify families in which there is evidence of genetic, transmission for OA and perform a series of studies comparing disease expression in families with genetic transmission to those without it. In this analysis we will characterize genetic OA by its joint involvement and severity and will evaluate whether genetically transmitted OA is likely to be associated with certain specific risk factors. The identification of families with OA will facilitate future linkage in studies and molecular genetic studies which can focus on inherited defects.

近年来，一个重要的遗传成分被认为是 许多常见的风湿性疾病，包括强直性脊柱炎， 类风湿性关节炎和痛风。有几个家庭患有严重的 与遗传相关的早期进行性骨关节炎 已发现的异常现象表明，骨关节炎也可能是 由于遗传性异常。尽管如此，这些家庭是不寻常的 目前尚不清楚普通人群中的骨性关节炎是否 经常是由于遗传异常，如果是的话，是什么模式 基因遗传才是。事实上，令人惊讶的是，几乎没有什么信息 关于人群中骨关节炎的遗传学。没有流行病学 关于骨性关节炎遗传性的研究曾在 北美。 这个项目的目标是研究人类遗传的本质。 通过观察广泛性骨关节炎与广泛性骨关节炎的关系 弗雷明汉队列及其后代中的疾病 子孙组。为了实现这一目标，我们将研究 手和膝盖都有的弗雷明翰后代群体的成员 队列中的父母之前被评估为骨性关节炎。 为了实现这些目标，我们将追求几个具体的目标 目标：1)我们将描述广泛性骨性关节炎及其已知的风险因素 在目标后代中；2)我们将阅读以前获得的手部x光片 来自OA的目标队列受试者，并描述了 队列受试者；3)使用复杂分离分析和调整 通过考虑年龄、性别和其他因素来评估患骨性关节炎的可能性 风险因素，我们将评估广泛性骨关节炎是否隔离在 并评估继承模式是否最适合单个 主基因模型(显性、共显性、隐性)，多因素模型， 混合模型(多因素背景下的单基因效应)或 不是按家庭进行汇总；以及4)我们将确定有哪些家庭 是遗传的证据，并进行了一系列的研究 比较有基因传播的家系中的疾病表现 没有它的话。在这项分析中，我们将通过其联合来描述遗传性骨性关节炎 参与程度和严重性，并将评估是否通过基因传播 骨质疏松症可能与某些特定的风险因素有关。这个 确认患有骨质疏松症的家庭将有助于今后在 可专注于遗传缺陷的研究和分子遗传学研究。