eCite Digital Repository

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

Citation

Rubio, JP and Stankovich, J and Field, J and Tubridy, N and Marriott, M and Chapman, C and Bahlo, M and Perera, DI and Johnson, LJ and Tait, BD and Varney, MD and Speed, TP and Taylor, BVM and Foote, SJ and Butzkueven, H and Kilpatrick, TJ, Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australians, Genes and Immunity, 9, (7) pp. 624-630. ISSN 1466-4879 (2008) [Refereed Article]

DOI: doi:10.1038/gene.2008.59

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 Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Neurology and Neuromuscular Diseases
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Inherited Diseases (incl. Gene Therapy)
UTAS Author:Stankovich, J (Dr Jim Stankovich)
UTAS Author:Perera, DI (Miss Devindri Perera)
UTAS Author:Taylor, BVM (Professor Bruce Taylor)
UTAS Author:Foote, SJ (Professor Simon Foote)
ID Code:53441
Year Published:2008
Web of Science® Times Cited:91
Deposited By:Menzies Institute for Medical Research
Deposited On:2008-12-09
Last Modified:2009-05-02
Downloads:0

Repository Staff Only: item control page