Replication study of GWAS risk loci in Greek multiple sclerosis patients

Neurol Sci. 2019 Feb;40(2):253-260. doi: 10.1007/s10072-018-3617-6. Epub 2018 Oct 26.

Abstract

Objectives: To validate in an ethnically homogeneous Greek multiple sclerosis (MS) cohort, genetic risk factors for the disease, identified through a number of previous multi-ethnic genome-wide association studies (GWAS).

Methods: A total of 1228 MS cases and 1014 controls were recruited in the study, from 3 MS centers in Greece. We genotyped 35 susceptibility SNPs that emerged from previous GWAS or meta-analyses of GWAS. Allele and genotype single locus regression analysis, adjusted for gender and site, was performed. Permutation testing was applied to all analyses.

Results: Six polymorphisms reached statistical significance (permutation p value < 0.05). In particular, rs2760524 of LOC105371664, near RGS1 (permutation p value 0.001), rs3129889 of HLA-DRA, near HLA-DRB1 (permutation p value < 1.00e-04), rs1738074 of TAGAP (permutation p value 0.007), rs703842 of METTL1/CYP27B1 (permutation p value 0.008), rs9596270 of DLEU1 (permutation p value < 1.00e-04), and rs17445836 of LincRNA, near IRF8 (permutation p value 0.001) were identified as susceptibility risk factors in our group.

Conclusion: The current study replicated a number of GWAS susceptibility SNPs, which implies that some similarities between the examined Greek population and the MS genetic architecture of the GWAS populations do exist.

Keywords: Genetic architecture; Genetic variants; Multiple sclerosis; Risk factors; SNPs; Susceptibility.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Greece
  • Humans
  • Male
  • Meta-Analysis as Topic
  • Middle Aged
  • Multiple Sclerosis / ethnology
  • Multiple Sclerosis / genetics*
  • Polymorphism, Single Nucleotide*
  • White People / genetics
  • Young Adult