Replication of CD58 and CLEC16A as genome-wide significant risk genes for multiple sclerosis
Replication of CD58 and CLEC16A as genome-wide significant risk genes for multiple sclerosis
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DOI：
10.1038/jhg.2009.96
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发表时间：
2009-11-01
影响因子：
3.5
通讯作者：
Hintzen, Rogier Q.
中科院分区：
文献类型：
--
作者：
Hoppenbrouwers, Ilse A.;Aulchenko, Yurii S.;Hintzen, Rogier Q.
国际多发性硬化遗传学联盟（IMSGC）最近的一项全基因组关联研究报告了14个位点的17个单核苷酸多态性（SNP）与多发性硬化（MS）的关联。只有两个位点，HLA-RA和IL 2 RA，达到全基因组显著性（P < 5E-08）。在我们的研究中，我们确定了我们是否可以复制IMSGC的结果，以及是否有更多的SNP在全基因组范围内与MS显著相关。我们评估了三个队列中17个IMSGC SNP与MS之间的关联（受试者总数为3981，其中1853例）。我们对我们的研究结果、原始IMSGC结果和最近在澳大利亚人群中进行的重复研究结果进行了荟萃分析。在17个IMSGC SNPs中，5个SNPs显示出与MS的全基因组显著相关性：HLA-HLA（P= 8 E-124）、IL 7 R（P= 6 E-09）、IL 2 RA（P= 1 E-11）、CD 58（P= 4 E-09）和CLEC 16 A（P=3E-12）。因此，全基因组的意义，现在已经显示在不同的非HLA MS风险基因的SNP。这些风险基因中的几个，包括CD 58和CLEC 16 A，由不同的自身免疫性疾病共享。精细定位研究将需要确定不同的自身免疫表型的功能贡献。Journal of Human Genetics（2009）54，676-680; doi：10.1038/jhg.2009.96; 2009年10月16日在线发表
A recent genome-wide association study by the International Multiple Sclerosis Genetics Consortium (IMSGC) reported association of 17 single-nucleotide polymorphisms (SNPs) in 14 loci with multiple sclerosis (MS). Only two loci, HLA-DRA and IL2RA, reached genome-wide significance (P < 5E-08). In our study, we determined whether we could replicate the results of the IMSGC and whether more SNPs are genome-wide significantly associated with MS. We assessed the association between the 17 IMSGC SNPs and MS in three cohorts (total number of subjects 3981, among these 1853 cases). We performed a meta-analysis of the results of our study, the original IMSGC results and the results of a recent replication study performed in the Australian population. Of the 17 IMSGC SNPs, five SNPs showed genome-wide significant association with MS: HLA-DRA (P=8E-124), IL7R (P=6E-09), IL2RA (P=1E-11), CD58 (P=4E-09) and CLEC16A (P=3E-12). Therefore, genome-wide significance has now been shown for SNPs in different non-HLA MS risk genes. Several of these risk genes, including CD58 and CLEC16A, are shared by different autoimmune diseases. Fine mapping studies will be needed to determine the functional contributions to distinct autoimmune phenotypes. Journal of Human Genetics (2009) 54, 676-680; doi:10.1038/jhg.2009.96; published online 16 October 2009