Unidad de Esclerosis Múltiple, Hospital Virgen Macarena, Sevilla, Spain.
PLoS One. 2012;7(5):e36140. doi: 10.1371/journal.pone.0036140. Epub 2012 May 3.
Multiple Sclerosis (MS) is the most common progressive and disabling neurological condition affecting young adults in the world today. From a genetic point of view, MS is a complex disorder resulting from the combination of genetic and non-genetic factors. We aimed to identify previously unidentified loci conducting a new GWAS of Multiple Sclerosis (MS) in a sample of 296 MS cases and 801 controls from the Spanish population. Meta-analysis of our data in combination with previous GWAS was done. A total of 17 GWAS-significant SNPs, corresponding to three different loci were identified:HLA, IL2RA, and 5p13.1. All three have been previously reported as GWAS-significant. We confirmed our observation in 5p13.1 for rs9292777 using two additional independent Spanish samples to make a total of 4912 MS cases and 7498 controls (ORpooled = 0.84; 95%CI: 0.80-0.89; p = 1.36 × 10-9). This SNP differs from the one reported within this locus in a recent GWAS. Although it is unclear whether both signals are tapping the same genetic association, it seems clear that this locus plays an important role in the pathogenesis of MS.
多发性硬化症（MS）是当今世界上最常见的影响年轻人的进行性和致残性神经疾病。从遗传角度来看，MS 是一种复杂的疾病，由遗传和非遗传因素共同作用引起。我们旨在通过对来自西班牙人群的 296 例 MS 病例和 801 例对照样本进行新的全基因组关联研究（GWAS），来确定以前未被识别的位点。对我们的数据进行荟萃分析，并结合以前的 GWAS 进行分析。总共确定了 17 个与 MS 相关的 GWAS 显著 SNP，对应三个不同的位点：HLA、IL2RA 和 5p13.1。所有三个位点以前都被报道为 GWAS 显著。我们使用另外两个独立的西班牙样本对 5p13.1 中的 rs9292777 进行了确认，总共纳入了 4912 例 MS 病例和 7498 例对照（ORpooled = 0.84；95%CI：0.80-0.89；p = 1.36 × 10-9）。该 SNP 与最近 GWAS 中报道的该位点的 SNP 不同。虽然尚不清楚这两个信号是否都涉及相同的遗传关联，但似乎可以清楚的是，该位点在 MS 的发病机制中起着重要作用。
