系统性硬皮病和系统性红斑狼疮全基因组关联研究揭示了新的共同易感位点。
A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci.
机构信息
These authors contributed equally to this work.
出版信息
Hum Mol Genet. 2013 Oct 1;22(19):4021-9. doi: 10.1093/hmg/ddt248. Epub 2013 Jun 4.
Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are two archetypal systemic autoimmune diseases which have been shown to share multiple genetic susceptibility loci. In order to gain insight into the genetic basis of these diseases, we performed a pan-meta-analysis of two genome-wide association studies (GWASs) together with a replication stage including additional SSc and SLE cohorts. This increased the sample size to a total of 21,109 (6835 cases and 14,274 controls). We selected for replication 19 SNPs from the GWAS data. We were able to validate KIAA0319L (P = 3.31 × 10(-11), OR = 1.49) as novel susceptibility loci for SSc and SLE. Furthermore, we also determined that the previously described SLE susceptibility loci PXK (P = 3.27 × 10(-11), OR = 1.20) and JAZF1 (P = 1.11 × 10(-8), OR = 1.13) are shared with SSc. Supporting these new discoveries, we observed that KIAA0319L was overexpressed in peripheral blood cells of SSc and SLE patients compared with healthy controls. With these, we add three (KIAA0319L, PXK and JAZF1) and one (KIAA0319L) new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity.
系统性硬化症（SSc）和系统性红斑狼疮（SLE）是两种典型的系统性自身免疫性疾病，它们被证明具有多个遗传易感基因座。为了深入了解这些疾病的遗传基础，我们对两项全基因组关联研究（GWAS）进行了泛亚荟萃分析，并在一个包含更多 SSc 和 SLE 队列的复制阶段进行了研究。这将样本量增加到总共 21109 例（6835 例病例和 14274 例对照）。我们从 GWAS 数据中选择了 19 个 SNP 进行复制。我们能够验证 KIAA0319L（P = 3.31×10（-11），OR = 1.49）是 SSc 和 SLE 的新易感基因座。此外，我们还确定了先前描述的 SLE 易感基因座 PXK（P = 3.27×10（-11），OR = 1.20）和 JAZF1（P = 1.11×10（-8），OR = 1.13）与 SSc 共享。支持这些新发现，我们观察到 KIAA0319L 在 SSc 和 SLE 患者的外周血细胞中表达高于健康对照。通过这些研究，我们分别为 SSc 和 SLE 增加了三个（KIAA0319L、PXK 和 JAZF1）和一个（KIAA0319L）新的易感基因座，大大增加了我们对自身免疫遗传基础的认识。
Zotero 插件