Identification of Susceptibility Genes for SLE of Amerindian Origin in Hispanics

西班牙裔美洲印第安人 SLE 易感基因的鉴定

• 批准号: 7943882
• 负责人: MARTA E ALARCON-RIQUELME
• 金额: $ 50万
• 依托单位: OKLAHOMA MEDICAL RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7943882
• 关键词: Address; Admixture; Affect; African American; Age; Age of Onset; Amerindian; Area; Authorization documentation; Autoimmune Diseases; Behavior; Chronic; Clinical; Complex; Controlled Study; DNA; Data; Development; Disease; Economic Factors; Environmental Hazards; Ethnic group; European; Foundations; Funding; Genes; Genetic; Genetic Risk; Genetic Variation; Genome; Genomics; Genotype; Hispanics; Individual; Inflammatory; International; Kidney; Lupus; Medical Research; Minority; Musculoskeletal Diseases; Native Americans; Oklahoma; Onset of illness; Organ; Pathogenesis; Patients; Play; Population; Principal Component Analysis; Publishing; Research Infrastructure; Risk; Role; Sampling; Skin; Social support; Staging; Susceptibility Gene; Systemic Lupus Erythematosus; Woman; case control; cohort; database of Genotypes and Phenotypes; genetic analysis; genetic association; genome wide association study; low socioeconomic status; socioeconomics

DESCRIPTION (provided by applicant): Item 6 Project Summary This application addresses broad Challenge Area (08) Genomics and Specific Challenge Topic, 08-AR-101 Genotyping Existing Cohorts in Rheumatic, Skin and Musculoskeletal Diseases. Systemic lupus erythematosus is not only primarily a disease of women, but it is also a disease affecting most severely women belonging to racial minorities. The reason for this is not clear, but there is evidence that it is two-fold: socio-economic and genetic. Indeed, studies have shown that patients of Hispanic ancestry develop SLE at a younger age, have a lower socio-economic status, have more organ involvement and more active disease combined with less social support and more abnormal illness-related behaviors. Further, Hispanic SLE patients have more abrupt onset of the disease and their social support is even lower than for African-American patients. Interestingly, studies have demonstrated that genetic factors, and in particular admixture, contribute more significantly to renal involvement in Hispanic patients than socio-economic factors, making the search for the identification of susceptibility genes of Amerindian origin in Hispanics an issue of urgency. We propose to perform a genome-wide association scan with large sets of cases and controls of Hispanic origin selected for the enrichment of two populations: European and Native American. Using whole-genome data, we will define the admixture through principal component analysis and the Amerindian contribution to the genetic risk for lupus. The best loci, within the framework of the funding will be selected for replication. This project will identify new loci for lupus of relevance in a minority population that suffers of a much more severe disease using cases and controls of enough statistical power and enriched for the appropriate Native American ancestry. All samples have, as for today, permission for immediate submission to dbGaP. Item 7. Project Narrative Lupus develops in women of Hispanic ancestry at a younger age, involves more organs, especially the kidneys. In our project, we will search for the identification of the genes associated with lupus in those of Amerindian origin in Hispanics. If we are lucky, then the advantages of Amerindian Hispanic ancestry will help us identify the exact changes in the DNA that help cause lupus.

描述（由申请人提供）：项目6项目摘要本申请涉及广泛的挑战领域（08）基因组学和特定的挑战主题，08-AR-101风湿性、皮肤和肌肉骨骼疾病中现有队列的基因分型。系统性红斑狼疮不仅主要是妇女的疾病，而且也是影响少数民族妇女最严重的疾病。其原因尚不清楚，但有证据表明，这是双重的：社会经济和遗传。事实上，研究表明，西班牙裔患者在更年轻的时候就患上了SLE，社会经济地位较低，器官受累较多，疾病活动性更强，社会支持较少，疾病相关行为异常较多。此外，西班牙裔SLE患者有更多的突然发病的疾病，他们的社会支持甚至低于非洲裔美国人的患者。有趣的是，研究表明，遗传因素，特别是混合物，有助于更显着的肾脏参与在西班牙裔患者比社会经济因素，使搜索确定美洲印第安人起源的易感基因在西班牙裔的一个紧迫的问题。我们建议进行一个全基因组关联扫描的情况下，选择了丰富的两个人口：欧洲和美洲原住民的西班牙裔血统的大型集和控制。使用全基因组数据，我们将通过主成分分析和美洲印第安人对狼疮遗传风险的贡献来定义混合物。将在资金框架内选择最佳地点进行复制。该项目将使用具有足够统计能力的病例和对照，在患有更严重疾病的少数人群中确定与狼疮相关的新位点，并为适当的美洲原住民祖先进行富集。从今天起，所有样本都可以立即提交给dbGaP。项目7.狼疮发生在西班牙裔女性中，年龄较轻，涉及更多器官，特别是肾脏。在我们的项目中，我们将寻找与狼疮相关的基因在美洲印第安人起源的西班牙裔美国人的识别。如果我们幸运的话，那么美洲印第安人西班牙裔血统的优势将帮助我们确定导致狼疮的DNA的确切变化。