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

Genes & Immunity volume 9, pages 624–630 (2008)Cite this 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 × 10−8) evidence of an association between KIAA0350 and risk of disease.

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Acknowledgements

We are grateful to people with MS who have participated in this study and to staff at The Royal Melbourne Hospital and Menzies Research Institute who were involved in recruitment of MS patients. JPR and MB are supported by Biomedical Career Development Awards from the Australian National Health and Medical Research Council (NHMRC). HB is supported by a Peter Doherty Post-doctoral Fellowship (NHMRC). SJF and TPS are Senior Principal Research Fellows of the NHMRC. This work was supported by Charity Works for MS, and an NHMRC Project grant (App ID 509184). The Broad Institute Center for Genotyping and Analysis is supported by grant U54 RR020278 from the National Center for Research Resources.

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Authors and Affiliations

  1. The Howard Florey Institute, Melbourne, Victoria, Australia

    J P Rubio, J Field, M Marriott, L J Johnson, H Butzkueven & T J Kilpatrick

  2. The Centre for Neuroscience, University of Melbourne, Melbourne, Victoria, Australia

    J P Rubio, H Butzkueven & T J Kilpatrick

  3. The Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia

    J Stankovich, D Perera, B V Taylor & S J Foote

  4. The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia

    J Stankovich, M Bahlo & T P Speed

  5. The Royal Melbourne Hospital, Melbourne, Victoria, Australia

    N Tubridy, M Marriott, C Chapman, H Butzkueven & T J Kilpatrick

  6. St Vincent's Healthcare Group, Dublin, Ireland

    N Tubridy

  7. The Australian Red Cross Blood Service, Melbourne, Victoria, Australia

    B D Tait & M D Varney

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  1. J P Rubio
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Correspondence to J P Rubio.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Rubio, J., Stankovich, J., Field, J. et al. Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australians. Genes Immun 9, 624–630 (2008). https://doi.org/10.1038/gene.2008.59

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  • DOI: https://doi.org/10.1038/gene.2008.59

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