Journal article
Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australian.
Genes and Immunity, Vol.9(7), pp.624-630
2008
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.
Details
- Title
- Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australian.
- Authors/Creators
- J.P. Rubio (Author/Creator)J. Stankovich (Author/Creator)J. Field (Author/Creator)N. Tubridy (Author/Creator)M. Marriott (Author/Creator)C. Chapman (Author/Creator)M. Bahlo (Author/Creator)D. Perera (Author/Creator)L.J. Johnson (Author/Creator)B.D. Tait (Author/Creator)M.D. Varney (Author/Creator)T.P. Speed (Author/Creator)B.V. Taylor (Author/Creator)S.J. Foote (Author/Creator)H. Butzkueven (Author/Creator)T.J. Kilpatrick (Author/Creator)
- Publication Details
- Genes and Immunity, Vol.9(7), pp.624-630
- Publisher
- Nature Publishing Group
- Identifiers
- 991005541098507891
- Copyright
- © 2008 Macmillan Publishers Limited, part of Springer Nature
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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Source: InCites
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.203 Neuromuscular Disorders
- 1.203.147 Multiple Sclerosis
- Web Of Science research areas
- Genetics & Heredity
- Immunology
- ESI research areas
- Molecular Biology & Genetics