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

Rubio, J.P., Stankovich, J., Field, J., Tubridy, N., Marriott, M., Chapman, C., Bahlo, M., Perera, D., Johnson, L.J., Tait, B.D., Varney, M.D., Speed, T.P., Taylor, B.V., Foote, S.J., Butzkueven, H. and Kilpatrick, T.J. (2008) Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australian. Genes and Immunity, 9 (7). pp. 624-630.

Link to Published Version: https://doi.org/10.1038/gene.2008.59
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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 × 10−8) evidence of an association between KIAA0350 and risk of disease.

Publication Type: Journal Article
Publisher: Nature Publishing Group
Copyright: © 2008 Macmillan Publishers Limited, part of Springer Nature
URI: http://researchrepository.murdoch.edu.au/id/eprint/38480
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