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Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australians.
Genes Immun 2008; 9(7):624-30GI

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.

Authors+Show Affiliations

The Howard Florey Institute, Melbourne, Victoria, Australia. justin.rubio@florey.edu.au

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18650830

Citation

Rubio, J P., et al. "Replication of KIAA0350, IL2RA, RPL5 and CD58 as Multiple Sclerosis Susceptibility Genes in Australians." Genes and Immunity, vol. 9, no. 7, 2008, pp. 624-30.
Rubio JP, Stankovich J, Field J, et al. Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australians. Genes Immun. 2008;9(7):624-30.
Rubio, J. P., Stankovich, J., Field, J., Tubridy, N., Marriott, M., Chapman, C., ... Kilpatrick, T. J. (2008). Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australians. Genes and Immunity, 9(7), pp. 624-30. doi:10.1038/gene.2008.59.
Rubio JP, et al. Replication of KIAA0350, IL2RA, RPL5 and CD58 as Multiple Sclerosis Susceptibility Genes in Australians. Genes Immun. 2008;9(7):624-30. PubMed PMID: 18650830.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australians. AU - Rubio,J P, AU - Stankovich,J, AU - Field,J, AU - Tubridy,N, AU - Marriott,M, AU - Chapman,C, AU - Bahlo,M, AU - Perera,D, AU - Johnson,L J, AU - Tait,B D, AU - Varney,M D, AU - Speed,T P, AU - Taylor,B V, AU - Foote,S J, AU - Butzkueven,H, AU - Kilpatrick,T J, Y1 - 2008/07/24/ PY - 2008/7/25/pubmed PY - 2009/11/11/medline PY - 2008/7/25/entrez SP - 624 EP - 30 JF - Genes and immunity JO - Genes Immun. VL - 9 IS - 7 N2 - 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. SN - 1476-5470 UR - https://www.unboundmedicine.com/medline/citation/18650830/Replication_of_KIAA0350_IL2RA_RPL5_and_CD58_as_multiple_sclerosis_susceptibility_genes_in_Australians_ L2 - http://dx.doi.org/10.1038/gene.2008.59 DB - PRIME DP - Unbound Medicine ER -