Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australians
Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australians
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DOI：
10.1038/gene.2008.59
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发表时间：
2008-10-01
影响因子：
5
通讯作者：
Kilpatrick, T. J.
中科院分区：
文献类型：
--
作者：
Rubio, J. P.;Stankovich, J.;Kilpatrick, T. J.
最近由国际多发性硬化遗传学联盟（IMSGC）进行的全基因组关联研究（GWAS）确定了许多推定的MS易感基因。在这里，我们进行了一项重复研究，在1134例澳大利亚MS病例和1265对照组的17个风险相关的单核苷酸多态性（SNPs）的IMSGC报告。在通过质量控制过滤器的16个SNP中，有4个与疾病易感性相关，每个对应于不同的非人类白细胞抗原（HLA）基因：KIAA0350（rs6498169）P = 0.001，IL2RA（rs2104286）P = 0.033，RPL 5（rs6604026）P = 0.041和CD58（rs12044852）P = 0.042。IL 7 R基因中的rs6897932与MS的风险之间没有关联（P=0.58）。在复制的IMSGC SNP与HLA-DRB 1 *15、性别、病程、疾病进展或发病年龄之间没有检测到相互作用。我们使用了一种新的贝叶斯方法来估计我们的数据增加或减少与六个最相关的IMSGC基因座相关的证据的程度。这些分析表明，即使是适度的P值，如这里报道的，可以显着贡献的后验概率的“真正的”关联在复制研究。总之，这些数据支持四个非HLA基因参与MS的发病机制，并结合以前的数据，增加了KIAA 0350和疾病风险之间的关联的全基因组显著性（P=3 × 10（-8））证据。
A recent genome-wide association study (GWAS) conducted by the International Multiple Sclerosis Genetics Consortium (IMSGC) identified a number of putative MS susceptibility genes. Here we have performed a replication study in 1134 Australian MS cases and 1265 controls for 17 risk-associated single nucleotide polymorphisms (SNPs) reported by the IMSGC. Of 16 SNPs that passed quality control filters, four, each corresponding to a different non-human leukocyte antigen (HLA) gene, were associated with disease susceptibility: KIAA0350 (rs6498169) P = 0.001, IL2RA (rs2104286) P = 0.033, RPL5 (rs6604026) P = 0.041 and CD58 (rs12044852) P = 0.042. There was no association (P=0.58) between rs6897932 in the IL7R gene and the risk of MS. No interactions were detected between the replicated IMSGC SNPs and HLA-DRB1*15, gender, disease course, disease progression or age-at-onset. We used a novel Bayesian approach to estimate the extent to which our data increased or decreased evidence for association with the six most-associated IMSGC loci. These analyses indicated that even modest P-values, such as those reported here, can contribute markedly to the posterior probability of 'true' association in replication studies. In conclusion, these data provide support for the involvement of four non-HLA genes in the pathogenesis of MS, and combined with previous data, increase to genome-wide significance (P=3 x 10(-8)) evidence of an association between KIAA0350 and risk of disease.