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. ; Journal Article; Meta-Analysis; Research Support, Non-U.S. Gov't; Funding: The Macarena MS project was supported by Neuroinvest, Carlos III, and Fonde de Investigaciones Sanitarias (FIS) grants. The project to collect and genotype the Spanish controls was supported in part by: Agencia IDEA, Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía (830882); Corporación Tecnológica de Andalucía (07/124); Ministerio de Educación y Ciencia (PCT-A41502790-2007 and PCT-010000-2007-18); Programa de Ayudas Torres Quevedo del Ministerio de Ciencia e Innovación (PTQ2002-0206, PTQ2003-0549, PTQ2003-0546, PTQ2003-0782, PTQ2003-0783, PTQ2004-0838, PTQ04-1-0006, PTQ04-3-0718, PTQ06-1-0002). CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) is an ISCIII project. The validation project was supported by Fondos Europeos de Desarrollo Regional (P09-CTS-5218 FEDER), Ministerio de Ciencia e Innovación (SAF2009-11491) to Dr. Alcina, and Fondo de Investigación Sanitaria (PI081636) to Dr. Matesanz, and FIS PI10/1985. Funding support for the IMSGC GWAS of Multiple Sclerosis and the Genetic Multiple Sclerosis Associations (GeneMSA) projects were provided by National Institutes of Health (NIH) and GlaxoSmithKline, respectively, and the genotyping of samples was provided by the National Institute of Neurological Disorders and Stroke (NINDS). Some of the datasets used for the analyses described in this manuscript were obtained from the NINDS Database found at http://www.ncbi.nlm.nih.gov/sites/entrez?db=gap through dbGaP accession numbers phs000139.v1.p1 and phs000171.v1.p1. This study also makes use of data generated by the Wellcome Trust Case-Control Consortium. A full list of the investigators who contributed to the generation of the data is available from www.wtccc.org.uk. Funding for the project was provided by the Wellcome Trust under awards 076113 and 085475. This Sardinian GWAS study was supported by the Fondazione Italiana Sclerosi Multipla (FISM) Cod. 2008/R/7 to Dr. Cucca, by the Italian Ministry of Scientific Research (MIUR grant 2007KXNKNP) and by US National Institutes of Health contract NO1-AG-1-2109 from National Institute of Aging (NIA) to the SardiNIA (‘ProgeNIA’) team. Sardinian GWAS authors are grateful to all cases and controls, and to the wide network of collaborators, clinicians and nurses of clinical and hospitals in the island. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.