Genetics, ancestry and SLE outcomes

遗传学、血统和 SLE 结果

基本信息

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.
SLE的流行病学研究早在1960年代就表明,SLE不仅更普遍,而且在少数民族中更为严重。随后的研究在遗传,环境或其他因素造成这些差异的程度上引起了激烈的争论。但是,大多数关于种族和SLE的流行病学研究将种族视为同质类别,从而消除了可能有助于观察到的差异的群体中存在的遗传,文化和社会经济多样性。在研究种族,遗传学和疾病特征时,使用遗传血统而不是自我识别的种族可提供一些优势。这种方法并不认为种族或种族是同质的,而是利用群体内部的遗传异质性,以更有效地剖析种族,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祖先和SLE疾病特征的遗传流行病学研究,并将利用一种新型工具“免疫光切”。这个独特的基因分型阵列由约200,000个遗传标记组成,这些标记被选中以提供最近确定的自身免疫基因基因座的详细覆盖范围,并且对于全面的遗传血统也很有帮助。拟议的项目将受益于广泛的协作网络,该网络支持UCSF狼疮结果研究(LOS)参与者和其他SLE同伙的表征,用于免疫遗传学标记集。 SES和其他有关LOS参与者的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,我们提出了以下目的:1)表征遗传血统之间的关系,包括大陆和洲际祖先,以及SLE疾病特征,包括SLE诊断时代的年龄,肾脏疾病,抗DSDNA自身抗体的产生和累积损害; 2)确定最近发现的遗传基因座是否从基因组广泛的关联和其他遗传研究中出现是特定SLE表现的风险因素。对于与特定SLE表现相关的基因变体,我们将表征这些变体在AIM 1中所证明的祖先关联的程度。该项目将通过阐明影响SLE中种族差异的更近端的因素来推进该领域,以及我们对健康差异的关注与我们的MCRC的整体主题相协调。

项目成果

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Lindsey Ann Criswell其他文献

Lindsey Ann Criswell的其他文献

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{{ truncateString('Lindsey Ann Criswell', 18)}}的其他基金

Resource-based Center for the Advancement of Precision Medicine in Rheumatology
风湿病精准医学推进资源中心
  • 批准号:
    9768155
  • 财政年份:
    2016
  • 资助金额:
    $ 15.35万
  • 项目类别:
Admin Core
管理核心
  • 批准号:
    10007630
  • 财政年份:
    2016
  • 资助金额:
    $ 15.35万
  • 项目类别:
Genetic and epigenetic contributions to Sjogren's syndrome
遗传和表观遗传对干燥综合征的影响
  • 批准号:
    8991063
  • 财政年份:
    2015
  • 资助金额:
    $ 15.35万
  • 项目类别:
Genetic and epigenetic contributions to Sjogren's syndrome
遗传和表观遗传对干燥综合征的影响
  • 批准号:
    8829521
  • 财政年份:
    2015
  • 资助金额:
    $ 15.35万
  • 项目类别:
Dissecting the HLA contribution to Rheumatoid Arthritis
剖析 HLA 对类风湿关节炎的贡献
  • 批准号:
    8094154
  • 财政年份:
    2010
  • 资助金额:
    $ 15.35万
  • 项目类别:
Refining The Complex HLA Association With SLE Across Ethnic And Phenotyping Subgr
完善 HLA 与 SLE 跨种族和表型亚群的复杂关联
  • 批准号:
    7774737
  • 财政年份:
    2009
  • 资助金额:
    $ 15.35万
  • 项目类别:
The Interplay of Sociodemographic and Genetic Factors in SLE Health Disparities
社会人口学和遗传因素在 SLE 健康差异中的相互作用
  • 批准号:
    7612004
  • 财政年份:
    2008
  • 资助金额:
    $ 15.35万
  • 项目类别:
The Interplay of Sociodemographic and Genetic Factors in SLE Health Disparities
社会人口学和遗传因素在 SLE 健康差异中的相互作用
  • 批准号:
    7492406
  • 财政年份:
    2007
  • 资助金额:
    $ 15.35万
  • 项目类别:
Genetics, ancestry and SLE outcomes
遗传学、血统和 SLE 结果
  • 批准号:
    9067805
  • 财政年份:
    2006
  • 资助金额:
    $ 15.35万
  • 项目类别:
Dissecting the HLA contribution to Rheumatoid Arthritis
剖析 HLA 对类风湿关节炎的贡献
  • 批准号:
    7102143
  • 财政年份:
    2006
  • 资助金额:
    $ 15.35万
  • 项目类别:

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类风湿关节炎患者全身炎症、心血管风险状况与阿尔茨海默病及相关痴呆症发展之间的时间关联
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