Neurogenomiks Laboratory, Department of Neuroscience, University of the Basque Country UPV/EHU, Leioa, Spain.
Genes Immun. 2012 Apr;13(3):253-7. doi: 10.1038/gene.2011.81. Epub 2011 Dec 1.
Multiple sclerosis (MS) shares some risk genes with other disorders hallmarked by an autoimmune pathogenesis, most notably IL2RA and CLEC16A. We analyzed 10 single-nucleotide polymorphisms (SNPs) in nine risk genes, which recently emerged from a series of non-MS genome-wide association studies (GWAS), in a Spanish cohort comprising 2895 MS patients and 2942 controls. We identified two SNPs associated with MS. The first SNP, rs6859219, located in ANKRD55 (Chr5), was recently discovered in a meta-analysis of GWAS on rheumatoid arthritis (RA), and emerged from this study with genome-wide significance (odds ratio (OR) = 1.35; P = 2.3 × 10(-9)). The second SNP, rs12785878, is located near DHCR7 (Chr11), a genetic determinant of vitamin D insufficiency, and showed a size effect in MS similar to that recently observed in Type 1 diabetes (T1D; OR = 1.10; P = 0.009). ANKRD55 is a gene of unknown function, and is flanked proximally by the IL6ST-IL31RA gene cluster. However, rs6859219 did not show correlation with a series of haplotype-tagging SNPs covering IL6ST-IL31RA, analyzed in a subset of our dataset (D'< 0.31; r(2)< 0.011). Our results expand the number of risk genes shared between MS, RA and T1D.
多发性硬化症（MS）与其他自身免疫性疾病有一些共同的风险基因，尤其是 IL2RA 和 CLEC16A。我们分析了 9 个风险基因中的 10 个单核苷酸多态性（SNP），这些基因最近从一系列非 MS 全基因组关联研究（GWAS）中出现，在一个包括 2895 名 MS 患者和 2942 名对照的西班牙队列中进行分析。我们确定了两个与 MS 相关的 SNP。第一个 SNP，rs6859219，位于 ANKRD55（Chr5），最近在类风湿关节炎（RA）GWAS 的荟萃分析中被发现，并在这项研究中具有全基因组意义（比值比（OR）= 1.35；P = 2.3×10(-9)）。第二个 SNP，rs12785878，位于 DHCR7（Chr11）附近，是维生素 D 不足的遗传决定因素，在 MS 中的大小效应与最近在 1 型糖尿病（T1D）中观察到的相似（OR = 1.10；P = 0.009）。ANKRD55 是一个功能未知的基因，其附近是 IL6ST-IL31RA 基因簇。然而，rs6859219 与我们数据集的一个亚集中分析的一系列覆盖 IL6ST-IL31RA 的单倍型标记 SNP 没有相关性（D'<0.31；r(2)<0.011）。我们的结果扩展了 MS、RA 和 T1D 之间共同的风险基因数量。
