Replication of top markers of a genome-wide association study in multiple sclerosis in Spain

Genes Immun. 2011 Mar;12(2):110-5. doi: 10.1038/gene.2010.52. Epub 2010 Oct 14.


Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with presumed autoimmune origin, triggered by genetic and environmental risk factors. A recent genome-wide association study conducted on MS identified new biallelic markers outside the HLA (human leucocyte antigen) region involved in disease susceptibility: rs1109670 (DDEF2); rs1458175 (PDZRN4); rs1529316 and rs2049306 (CSMD1); rs16914086 (TBC1D2); rs1755289 (SH3GL2); rs1841770 (ZIC1); rs651477 (EN1); rs7607490 (TRIB2); rs397020 (C20orf46); rs908821 (SLC25A36); rs7672826 (MGC45800) and rs9523762 (GPC5). We aimed at replicating these top association signals in a Spanish cohort of 2863 MS patients and 2930 sex- and age-matched controls. Only rs9523762 mapping in the GPC5 gene was significantly associated (G allele, P=1.6 × 10(-5); odds ratio (95% confidence interval)=1.23 (1.12-1.36)), supporting a role for this proteoglycan in MS predisposition. The independent replication of association signals to validate data generated by genome-wide association scans is a first step in the effort to improve patient care.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Case-Control Studies
  • Cohort Studies
  • DNA Replication / genetics
  • Female
  • Gene Frequency / genetics
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • HLA Antigens / genetics
  • Humans
  • Male
  • Multiple Sclerosis / genetics*
  • Multiple Sclerosis / immunology
  • Spain


  • Genetic Markers
  • HLA Antigens