Defining teh Spectrum of Spondyloarthritis in Family Members of Patients w/AS

强直性脊柱炎（AS），最常见的定义为脊柱关节炎的疾病亚组 (SpA)包括以血清阴性中轴和/或外周关节炎为特征的疾病谱， 家族聚集性，重叠的粘膜皮肤和内脏特征，以及与基因的关联， 主要组织相容性复合体（MHC），包括HLA-B27。许多看似不同但又相互关联的 该组中的疾病包括AS、急性前葡萄膜炎（AAU）、炎性肠病（IBD）和 银屑病关节炎（PsA）、反应性关节炎（ReA）和未分化脊柱关节炎（uSpA）。大 许多研究已经定义了AS和其他SpA的家族聚集性，但结果往往是 自相矛盾，缺乏任何一致的遗传易感因素，部分原因是临床偏见， 由于患者或家系数量少，最近有一个 越来越多的人认为SpA本身可能是由特定的遗传因素引起的，而其他基因 相互作用，导致特定表型的发展（即葡萄膜炎，IBD或银屑病）。定义这些 这些因素不仅为SpA本身的发病机制提供线索， 这不仅是一个问题，也是一个问题， 与这些表现相关的疾病。在这个项目中，我们假设有特定的 易患SpA的基因，与其他基因相互作用产生特定的表型表现 (i.e.银屑病、葡萄膜炎、IBD等）。为了检验这一假设，我们将（1）定义患病率， 脊柱关节炎的一级亲属（FDR）中明确定义的表型表达模式 目的2：明确SpA异质性的特殊遗传结构 通过传统的遗传分析方法和新的设计， 系统生物学方法如项目4中所定义。约翰·戴维斯博士将担任首席研究员， Michael Weismans博士将担任该项目的共同主要研究者。戴维斯博士和魏斯曼博士 具有SpA患者临床研究和临床护理领域的专业知识。此外，我们将 与项目1（Reveille博士）、项目2（Weisman博士和Ward博士）和项目4（Lin博士和 Xiong）。林博士和熊博士在基因分析和统计建模方面都有专业知识， 执行。研究协调将由两名协调员进行。在加州大学旧金山分校，斯蒂芬妮摩根将 协调75%的项目行政支持。此外，雪松西奈医疗中心的一名协调员 中心将为研究提供25%的工作量。我们也将有米里亚姆比安科在脊椎炎的帮助 美国患者招募和数据收集协会。

Ankylosing spondylitis (AS),the most common defined subgroup of diseases known as spondyloarthritis (SpA), includes a spectrum of disease characterized by a seronegative axial and/or peripheral arthritis with familial clustering, overlapping mucocutaneous and visceral features, and associations with genes in the major histocompatibility complex (MHC), including HLA-B27. Many seemingly distinct but inter-related diseases in this group include AS, acute anterior uveitis (AAU), inflammatory bowel disease (IBD) and psoriatic arthritis (PsA), reactive arthritis (ReA), and undifferentiated spondyloarthritis (uSpA). A large number of studies have defined familial aggregation in AS and other SpA, however the findings are often contradictory and lacking in any consistent genetic predisposing factors, due in part to biases in clinical ascertainment or to power concerns due to small numbers of patients or pedigrees. There is a recent growing trend to consider that SpA per se may be caused by specific genetic factors with which other genes interact to cause the development of specific phenotypes (i.e. uveitis, IBD or psoriasis). Defining these factors would be valuable in not only in providing clues to the pathogenesis of SpA itself and in specific manifestations thereof, but also in designing generic or specific interventions that could reduce the morbidities associated with these manifestations. In this project, we hypothesize that there are specific genes that predispose to SpA, with which other genes interact to produce specific phenotypic manifestations (i.e. psoriasis, uveitis, IBD, etc). In order to test this hypothesis, we will (1) define the prevalence and patterns of well-defined phenotype expression of spondyloarthritis in the first degree relatives (FDRs) of patients with AS, and (2) Aim 2: define the specific genetic architecture of the heterogeneity of SpA phenotypes in the FDR of probands with AS by traditional genetic analysis methods and novel designs using systems biology approach as defined in Project 4. Dr John Davis will serve as the Principal Investigator on this project and Dr. Michael Weismans will serve as a Co-Principal Investigator. Drs. Davis and Weisman have expertise in the area of clinical research and clinical care in patients with SpA. In addition, we will collaborate with investigators on Projects 1 (Dr. Reveille), 2 (Dr. Weisman and Ward), and 4 (Drs. Lin and Xiong). Drs. Lin and Xiong have expertise in both the genetic analyses and statistical modeling to be performed. Study coordination will be performed by two coordinators. At UCSF, Stephanie Morgan will coordinate 75% of the project administrative support. In addition, a coordinator at Cedar Sinai Medical Center will provide 25% effort to the study. We will also have the help of Myriam Bianco at the Spondylitis Association of America for patient recruitment and data collection.