Tag-SNP analysis of the GFI1-EVI5-RPL5-FAM69 risk locus for multiple sclerosis.
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.
Alcina
Antonio
A
Instituto de Parasitología y Biomedicina López Neyra, Consejo Superior de Investigaciones Científicas, Granada, Spain.
Fernández
Oscar
O
Gonzalez
Juan Ramón
JR
Catalá-Rabasa
Antonio
A
Fedetz
María
M
Ndagire
Dorothy
D
Leyva
Laura
L
Guerrero
Miguel
M
Arnal
Carmen
C
Delgado
Concepción
C
Lucas
Miguel
M
Izquierdo
Guillermo
G
Matesanz
Fuencisla
F
D000328:Adult; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020690:GTPase-Activating Proteins; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012044:Regression Analysis; D012269:Ribosomal Proteins / Q000235:genetics*; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C506399:EVI5 protein, human; C498275:GFI1 protein, human; D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; D012269:Ribosomal Proteins; D014157:Transcription Factors; C549166:ribosomal protein L5, human