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

• Published in: European journal of human genetics : EJHG 2010-07, Vol.18 (7), p.827-831
• Main Authors: Alcina, Antonio, Fernández, Óscar, Gonzalez, Juan Ramón, Catalá-Rabasa, Antonio, Fedetz, María, Ndagire, Dorothy, Leyva, Laura, Guerrero, Miguel, Arnal, Carmen, Delgado, Concepción, Lucas, Miguel, Izquierdo, Guillermo, Matesanz, Fuencisla
• Format: Article
• Language: English
• Subjects: 631/208/205/2138; 631/208/457/649; 692/699/2743/1313/1666; Adult; Bioinformatics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Blood & organ donations; Case-Control Studies; Cell cycle; Consortia; Cytogenetics; Cytokines; DNA-Binding Proteins - genetics; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene mapping; General aspects. Genetic counseling; Genes; Genetic Loci - genetics; Genetic Predisposition to Disease; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genome-Wide Association Study; Genomes; Genomics; Genotyping; Human Genetics; Humans; Linkage disequilibrium; Linkage Disequilibrium - genetics; Male; Medical genetics; Medical sciences; Molecular and cellular biology; Multiple sclerosis; Multiple Sclerosis - genetics; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Nuclear Proteins - genetics; Polymorphism, Single Nucleotide - genetics; Power; Proteins; Regression Analysis; Ribosomal Proteins - genetics; Risk Factors; Sclerosis; Single-nucleotide polymorphism; Transcription Factors - genetics
• ISSN: 1018-4813; 1476-5438
• DOI: 10.1038/ejhg.2009.240

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 ( r 2 =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.