Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australians

Rubio, JP; Stankovich, J; Field, J; Tubridy, N; Marriott, M; Chapman, C; Bahlo, M; Perera, D; Johnson, LJ; Tait, BD; Varney, MD; Speed, TP; Taylor, BV; Foote, SJ; Butzkueven, H; Kilpatrick, TJ

Author(s): Rubio, JP; Stankovich, J; Field, J; Tubridy, N; Marriott, M; Chapman, C; Bahlo, M; Perera, D; Johnson, LJ; Tait, BD; Varney, MD; Speed, TP; Taylor, BV; Foote, SJ; Butzkueven, H; Kilpatrick, TJ;
Details: Publication Year 2008-10,Volume 9,Issue #7,Page 624-630
Journal Title: GENES AND IMMUNITY
Publication Type: Journal Article
Abstract: A recent genome-wide association study (GWAS) conducted by the International Multiple Sclerosis Genetics Consortium (IMSGC) identified a number of putative MS susceptibility genes. Here we have performed a replication study in 1134 Australian MS cases and 1265 controls for 17 risk-associated single nucleotide polymorphisms (SNPs) reported by the IMSGC. Of 16 SNPs that passed quality control filters, four, each corresponding to a different non-human leukocyte antigen (HLA) gene, were associated with disease susceptibility: KIAA0350 (rs6498169) P = 0.001, IL2RA (rs2104286) P = 0.033, RPL5 (rs6604026) P = 0.041 and CD58 (rs12044852) P = 0.042. There was no association (P=0.58) between rs6897932 in the IL7R gene and the risk of MS. No interactions were detected between the replicated IMSGC SNPs and HLA-DRB1*15, gender, disease course, disease progression or age-at-onset. We used a novel Bayesian approach to estimate the extent to which our data increased or decreased evidence for association with the six most-associated IMSGC loci. These analyses indicated that even modest P-values, such as those reported here, can contribute markedly to the posterior probability of 'true' association in replication studies. In conclusion, these data provide support for the involvement of four non-HLA genes in the pathogenesis of MS, and combined with previous data, increase to genome-wide significance (P=3 x 10(-8)) evidence of an association between KIAA0350 and risk of disease.
Publisher: NATURE PUBLISHING GROUP
Keywords: CLASS-I REGION; INTERLEUKIN-7 RECEPTOR; DIAGNOSTIC-CRITERIA; HLA COMPLEX; RISK; ASSOCIATION; HAPLOTYPES; LOCUS; POLYMORPHISMS; TASMANIANS
Publisher's Version: https://doi.org/10.1038/gene.2008.59
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2008-10-01 12:00:00