Meta-analysis Followed by Replication Identifies Loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as Associated with Systemic Lupus Erythematosus in Asians
Meta-analysis Followed by Replication Identifies Loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as Associated with Systemic Lupus Erythematosus in Asians
复制标题
荟萃分析和复制确定了 CDKN1B、TET3、CD80、DRAM1 和 ARID5B 中或附近的位点与亚洲人系统性红斑狼疮相关。
DOI：
10.1016/j.ajhg.2012.11.018
复制
发表时间：
2013-01-10
影响因子：
9.8
通讯作者：
Lau, Yu Lung
中科院分区：
文献类型：
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作者：
Yang, Wanling;Tang, Huayang;Lau, Yu Lung
系统性红斑狼疮（SLE）是一种典型的自身免疫性疾病，具有很强的遗传参与和种族差异。目前发现的易感基因仅解释了SLE遗传的一小部分，这表明更多的基因位点尚未被发现。在这项研究中，我们对中国汉族人群中SLE的全基因组关联研究进行了荟萃分析，并通过在另外4个亚洲队列中重复研究对结果进行了随访，共有5，365例病例和10，054例相应对照。我们确定了CDKN1B、TET3、CD80、DRAM 1和ARID5B中或附近的遗传变异与该疾病相关。这些发现指出了细胞周期调控、自噬和DNA去甲基化在SLE发病机制中的潜在作用。对于涉及TET3和涉及CDKN1B的区域，确定了多个独立的SNP，突出了一种可能部分解释复杂疾病遗传性缺失的现象。
Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases.