Identification of Susceptibility Genes for SLE of Amerindian Origin in Hispanics

本申请涉及广泛的挑战领域（08）基因组学和特定挑战主题，08- ar -101风湿病、皮肤和肌肉骨骼疾病现有队列的基因分型。系统性红斑狼疮不仅主要是一种妇女疾病，而且也是一种对少数民族妇女影响最严重的疾病。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SLE患者发病年龄更小，社会经济地位更低，器官受累更多，疾病更活跃，社会支持更少，疾病相关异常行为更多。此外，西班牙裔SLE患者发病更为突然，其社会支持甚至低于非裔美国患者。有趣的是，研究表明，与社会经济因素相比，遗传因素，尤其是混合因素，对西班牙裔患者肾脏受累的影响更大，这使得寻找西班牙裔美国印第安人血统的易感基因成为当务之急。我们建议对西班牙裔的大量病例和对照进行全基因组关联扫描，以丰富两个人群：欧洲人和美洲原住民。利用全基因组数据，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这种混合。将在资助范围内选择最佳基因座进行复制。该项目将利用足够统计能力的病例和对照，在患有严重得多疾病的少数人群中发现与狼疮相关的新位点，并为适当的美洲原住民血统进行充实。到目前为止，所有示例都允许立即提交给dbGaP。7项。红斑狼疮发生于西班牙裔女性，发病年龄较小，涉及更多器官，尤其是肾脏。在我们的项目中，我们将在西班牙裔美洲印第安人中寻找与狼疮相关的基因。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。

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.