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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.auNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

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 -