Fuencisla Matesanz, Antonio González-Pérez, Miguel Lucas, Serena Sanna, Javier Gayán, Elena Urcelay, Ilenia Zara, Maristella Pitzalis, María L. Cavanillas, Rafael Arroyo, Magdalena Zoledziewska, Marisa Marrosu, Oscar Fernández, Laura Leyva, Antonio Alcina, Maria Fedetz, Concha Moreno-Rey, Juan Velasco, Luis M. Real, Juan Luis Ruiz-Peña, Francesco Cucca, Agustín Ruiz, Guillermo Izquierdo

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.