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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.

Item Type:	Article
Authors/Creators:	Rubio, JP and Stankovich, J and Field, J and Tubridy, N and Marriott, M and Chapman, C and Bahlo, M and Perera, D and Johnson, LJ and Tait, BD and Varney, MD and Speed, TP and Taylor, BV and Foote, SJ and Butzkueven, H and Kilpatrick, TJ
Keywords:	multiple sclerosis; replication; susceptibility; Australia
Journal or Publication Title:	Genes and Immunity
ISSN:	1466-4879
DOI / ID Number:	10.1038/gene.2008.59
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