HEREDITY IN OSTEOARTHRITIS--FARMINGTON OFFSPRING

骨关节炎的遗传——法明顿后代

• 批准号: 5206105
• 负责人: DAVID T FELSON
• 金额: --
• 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/5206105
• 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，人们认识到， 许多常见的风湿性疾病，包括强直性脊柱炎， 风湿性关节炎和痛风。 几个严重的家庭， 进行性骨关节炎在早期的年龄和相关的遗传 已经发现异常，这表明骨关节炎也可能是 因为遗传性异常 尽管如此，这些家庭是不寻常的 目前还不清楚骨关节炎是否在人群中普遍存在， 通常是由于遗传异常，如果是这样， 基因遗传。 事实上，关于这个问题的信息 关于人群中骨关节炎的遗传学。 无流行病学 骨关节炎的遗传性研究曾在 北美 本项目的目的是研究遗传的性质， 通过观察全身性骨关节炎与 在Frachial队列中的疾病和Frachial队列中的后代 后代群体 为了实现这一目标，我们将研究 在Fragrance后代组中， 先前评估为OA的队列中的父母。 为了实现这些目标，我们将 几个具体 目的：1）我们将描述广义OA和已知的风险因素， 在目标后代中; 2）我们将阅读先前获得的手部X光片 从OA的目标队列受试者中， 队列受试者; 3）使用复杂分离分析并调整 骨关节炎的可能性，考虑到年龄，性别，和其他 风险因素，我们将评估泛发性OA是否在 家庭和评估是否继承模式最适合一个单一的 主基因模型（显性、共显性、隐性），多因子模型， 混合模型（多因素背景下的单基因效应）或 不聚集在家庭;和4）我们将确定家庭，其中有 是遗传的证据，传播为OA，并进行了一系列的研究 将遗传传播的家庭中的疾病表达与 在这项分析中，我们将通过其关节炎的联合特征来描述遗传性OA。 参与和严重程度，并将评估是否遗传传播 OA可能与某些特定的风险因素有关。 的 确定患有OA的家庭将有助于未来的联系， 研究和分子遗传学研究，可以集中在遗传缺陷。