Genetics, ancestry and SLE outcomes

遗传学、血统和 SLE 结果

基本信息

批准号：
8293902
负责人：
Lindsey Ann Criswell
金额：
$ 15.35万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-04-20 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8293902
关键词：
Accounting Age Autoimmune Diseases Autoimmune Process Autoimmunity Categories Caucasians Caucasoid Race Clinical Clinical Research Collaborations Development Diagnosis Disease Epidemiologic Studies Ethnic Origin Ethnic group European Genes Genetic Genetic Heterogeneity Genetic Markers Genetic Polymorphism Genetic Variation Genotype Hereditary Disease Heterogeneity ITGAM gene International Kidney Kidney Diseases Lupus National Institute of Arthritis and Musculoskeletal and Skin Diseases Other Genetics Outcome Outcome Study Participant Patients Play Production Race Research Research Personnel Research Support Rheumatism Risk Risk Factors Role STAT4 gene Serotyping Severities Socioeconomic Status Systemic Lupus Erythematosus Testing United States Variant Work anti-dsDNA autoantibody cohort design disease characteristic disorder risk disorder subtype ethnic difference ethnic minority population experience genetic resource genome wide association study health disparity improved interdisciplinary approach multidisciplinary non-genetic novel socioeconomics tool

项目摘要

Epidemiologic studies of SLE performed as early as the 1960s have noted that SLE is not only more common, but also more severe among ethnic minority populations. Subsequent studies have generated vigorous debate over the extent to which genetic, environmental or other factors account for these differences. However, most epidemiologic studies of ethnicity and SLE treat ethnic groups as homogeneous categories, thus obliterating the genetic, cultural, and socioeconomic diversity that exists within groups that could contribute to the observed differences. Using genetic ancestry rather than self-identified ethnicity provides some advantages when investigating ethnicity, genetics, and disease characteristics. This approach does not assume that racial or ethnic groups are homogeneous but rather capitalizes on genetic heterogeneity within groups to more effectively dissect the relationship between ethnicity, genetics, and disease risk. The proposed project is designed to extend our genetic epidemiologic investigations of ancestry and SLE disease characteristics and will take advantage of a novel tool, the "ImmunoChip". This unique genotyping array is comprised of ~200,000 genetic markers which were selected to provide detailed coverage of recently identified autoimmunity gene loci, and are also informative for comprehensive genetic ancestry. The proposed project will benefit from an extensive collaborative network, which has supported characterization of the UCSF Lupus Outcome Study (LOS) participants, and other SLE cohorts, for the ImmunoChip genetic marker set. The availability of SES and other covariate information on LOS participants will allow us to control for these potentially important factors in our analyses. More specifically, we are proposing the following aims: 1) characterize the relationship between genetic ancestry, including both continental and intra-continental ancestry, and SLE disease characteristics, including age at SLE diagnosis, renal disease, anti-dsDNA autoantibody production, and cumulative damage; and 2) determine whether recently identified genetic loci emerging from genome wide association and other genetic studies are risk factors for specific SLE manifestations. For gene variants associated with specific SLE manifestations, we will characterize the extent to which these variants explain ancestry associations demonstrated in Aim 1. This project will advance the field by elucidating more proximate factors that influence ethnic disparities in SLE, and our focus on health disparities synergizes well with the overall theme of our MCRC.

早在 20 世纪 60 年代就进行的 SLE 流行病学研究表明，SLE 在少数族裔人群中不仅更为常见，而且更为严重。随后的研究引发了关于遗传、环境或其他因素在多大程度上解释这些差异的激烈争论。然而，大多数关于种族和 SLE 的流行病学研究将种族群体视为同质类别，从而消除了群体内存在的遗传、文化和社会经济多样性，而这些多样性可能导致观察到的差异。在调查种族、遗传学和疾病特征时，使用遗传血统而不是自我认定的种族可以提供一些优势。这种方法并不假设种族或族裔群体是同质的，而是利用群体内的遗传异质性来更有效地剖析种族、遗传学和疾病风险之间的关系。拟议的项目旨在扩展我们对血统和 SLE 疾病特征的遗传流行病学调查，并将利用一种新工具“免疫芯片”。这种独特的基因分型阵列由约 200,000 个遗传标记组成，这些标记被选择来提供最近识别的自身免疫基因位点的详细覆盖范围，并且还为全面的遗传祖先提供信息。拟议的项目将受益于广泛的合作网络，该网络支持对免疫芯片遗传标记集的 UCSF 狼疮结果研究 (LOS) 参与者和其他 SLE 队列进行表征。 SES 和 LOS 参与者的其他协变量信息的可用性将使我们能够在分析中控制这些潜在的重要因素。更具体地说，我们提出以下目标：1）描述遗传血统（包括大陆和大陆内血统）与 SLE 疾病特征（包括 SLE 诊断年龄、肾脏疾病、抗 dsDNA 自身抗体产生和累积）之间的关系。损害; 2) 确定最近从全基因组关联和其他遗传学研究中发现的遗传位点是否是特定 SLE 表现的危险因素。对于与特定 SLE 表现相关的基因变异，我们将描述这些变异在多大程度上解释目标 1 中证明的血统关联。该项目将通过阐明影响 SLE 种族差异的更直接因素以及我们对健康差异的关注来推进该领域的发展与我们 MCRC 的整体主题很好地契合。