A genome-wide study of lupus preliminary analysis and data release
A genome-wide study of lupus preliminary analysis and data release
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DOI：
10.1196/annals.1423.015
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发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
Hoffman, Robert W.
中科院分区：
文献类型：
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作者：
Cervino, Alessandra C. L.;Tsinoremas, Nicholas E.;Hoffman, Robert W.
系统性红斑狼疮（SLE）是一种复杂的自身免疫性疾病，遗传学是其潜在的危险因素之一。使SLE分析复杂化的事实是，表型是异质性的，具有临床特征的变化，并且亚组与各种不同的自身抗体相关。许多候选基因的关联研究以及连锁研究已经产生了重要的结果，突出了疾病的多遗传成分。这些发现需要由独立的实验室重复，许多其他基因仍有待确定。在这里，我们提出了我们的研究结果的第一个全基因组的关联研究中进行的105例高加索患者和对照使用AffytoNspI阵列。在这里研究的SLE患者的特点都是对U1-6小核核糖核蛋白抗原剪接体复合物的自身抗体的存在。单独测试每个SNP与疾病的相关性，我们鉴定了7个标记物，未校正的P值< 0.0001。其中3个位于报告的连锁区域，即20 p12，2 q37和4p 15。为了增加我们研究的效力，我们纳入了60个对照组，这些对照组对应于来自公开的CEPH家族的父母。对165例病例和对照的分析导致28个SNP与未校正的P值< 0.0001相关。
Systemic lupus erythematosus (SLE) is a complex autoimmune disease in which genetics is one of the underlying risk factors. Complicating the analysis of SLE is the fact that the phenotype is heterogeneous, with variations in clinical features, and subgroups are associated with a variety of different autoantibodies. Many association studies of candidate genes as well as linkage studies have generated significant results, highlighting the multigenetic component of the disease. Those findings need to be replicated by independent laboratories and many other genes still remain to be identified. Here, we present our findings on the first genome-wide association study performed in 105 Caucasian patients and controls using the Affymetrix NspI array. The SLE patients studied here were all characterized by the presence of autoantibodies against the U1-6 small nuclear ribonucleoprotein antigen spliceosomal complex. Testing each SNP individually for association with disease, we identified 7 markers with an uncorrected P-value < 0.0001. Of those, three were in reported regions of linkage, namely 20p12, 2q37, and 4p15. To increase the power of our study, we included 60 controls corresponding to the parents from the publicly available CEPH families. The analysis of the 165 cases and controls leads to 28 SNPs being associated with an uncorrected P-value < 0.0001.