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Tag-SNP analysis of the GFI1-EVI5-RPL5-FAM69 risk locus for multiple sclerosis
Authors:Antonio Alcina  óscar Fernández  Juan Ramón Gonzalez  Antonio Catalá-Rabasa  María Fedetz  Dorothy Ndagire  Laura Leyva  Miguel Guerrero  Carmen Arnal  Concepción Delgado  Miguel Lucas  Guillermo Izquierdo  Fuencisla Matesanz
Abstract: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 eight Tag-SNPs in 732 MS patients and 974 controls from Spain. We observed an association with MS in three of eight 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 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 the EVI5 gene. Our findings agree with the corresponding data of the recent IMSGC study and present new genetic evidence that points to EVI5 as a factor of susceptibility to MS.
Keywords:Multiple sclerosis  Tag-SNP analysis  polymorphisms  GFI1-EVI5-RPL5-FAM69A genes  association  GWAS
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