Tag-SNP analysis of the GFI1-EVI5-RPL5-FAM69 risk locus for multiple sclerosis

Fuencisla Matesanz (1) , Antonio Alcina (1) , Oscar Fernández (1) , Juan R González (1) , Antonio Catalá-Rabasa (1) , Maria Fedetz (1) , Dorothy Ndagire (1) , Laura Leyva (1) , Miguel Guerrero (1) , Carmen Arnal (1) , Concepción Delgado (1) , Miguel Lucas (1) , Guillermo Izquierdo (1)

1 Cell Biology and Immunology

A recent genome-wide association study conducted by the International Multiple Sclerosis Genetic Consortium (IMSGC) identified, among others, a number of putative multiple sclerosis (MS) susceptibility variants at position 1p22. Twenty one SNPs positively associated with MS were located at the GFI -EVI5-RPL5-FAM69A locus. In this study, we performed an analysis and fine mapping of this locus genotyping 8 Tag-SNPs up to 732 MS patients and 974 controls from Spain. We observed association with MS in 3 of 8 Tag-SNPs: rs11804321 (P=0.008. OR=1.29; 95% CI=1.08-1.54), rs11808092 (P=0.048. OR=1.19; 95% CI=1.03-1.39) and rs6680578 (P=0.0082. OR=1.23; 95% CI=1.07-1.41). After correcting for multiple comparisons and using logistic regression analysis to test the addition of each SNP to the most associated SNPs, we observed that the rs11804321 alone was sufficient to model the association. This Tag-SNP captures two SNPs in complete linkage disequilibrium (r2 = 1) both located within the 17th intron of EVI5 gene. Our findings agree with the corresponding data of the recent IMSGC study and present new genetic evidence that point to EVI5 as a factor of susceptibility to MS.

Mots clés: Multiple sclerosis (MS); GFI1-EVI5-RPL5-FAM69A genes; SNPs

Fuencisla Matesanz, Antonio Alcina, Oscar Fernández, Juan R González, Antonio Catalá-Rabasa, et al.. Tag-SNP analysis of the GFI1-EVI5-RPL5-FAM69 risk locus for multiple sclerosis. European Journal of Human Genetics, 2010, n/a (n/a), pp.n/a-n/a. ⟨10.1038/ejhg.2009.240⟩. ⟨hal-00504138⟩