Journal article
Genetic loci for Epstein-Barr virus nuclear antigen-1 are associated with risk of multiple sclerosis
Multiple Sclerosis Journal, Vol.22(13), pp.1655-1664
2016
Abstract
BACKGROUND:
Infection with the Epstein-Barr virus (EBV) is associated with an increased risk of multiple sclerosis (MS).
OBJECTIVE:
We sought genetic loci influencing EBV nuclear antigen-1 (EBNA-1) IgG titers and hypothesized that they may play a role in MS risk.
METHODS:
We performed a genome-wide association study (GWAS) of anti-EBNA-1 IgG titers in 3599 individuals from an unselected twin family cohort, followed by a meta-analysis with data from an independent EBNA-1 GWAS. We then examined the shared polygenic risk between the EBNA-1 GWAS (effective sample size (Neff) = 5555) and a large MS GWAS (Neff = 15,231).
RESULTS:
We identified one locus of strong association within the human leukocyte antigen (HLA) region, of which the most significantly associated genotyped single nucleotide polymorphism (SNP) was rs2516049 (p = 4.11 × 10-9). A meta-analysis including data from another EBNA-1 GWAS in a cohort of Mexican-American families confirmed that rs2516049 remained the most significantly associated SNP (p = 3.32 × 10-20). By examining the shared polygenic risk, we show that the genetic risk for elevated anti-EBNA-1 titers is positively correlated with the development of MS, and that elevated EBNA-1 titers are not an epiphenomena secondary to MS. In the joint meta-analysis of EBNA-1 titers and MS, loci at 1p22.1, 3p24.1, 3q13.33, and 10p15.1 reached genome-wide significance (p < 5 × 10-8).
CONCLUSIONS:
Our results suggest that apart from the confirmed HLA region, the association of anti-EBNA-1 IgG titer with MS risk is also mediated through non-HLA genes, and that studies aimed at identifying genetic loci influencing EBNA immune response provides a novel opportunity to identify new and characterize existing genetic risk factors for MS.
Details
- Title
- Genetic loci for Epstein-Barr virus nuclear antigen-1 are associated with risk of multiple sclerosis
- Authors/Creators
- Y. Zhou (Author/Creator) - Menzies Research InstituteG. Zhu (Author/Creator) - QIMR Berghofer Medical Research InstituteJ.C. Charlesworth (Author/Creator) - Menzies Research InstituteS. Simpson (Author/Creator) - Menzies Research InstituteR. Rubicz (Author/Creator) - Fred Hutch Cancer CenterH.H.H. Göring (Author/Creator) - The University of Texas Rio Grande ValleyN.A. Patsopoulos (Author/Creator) - Brigham and Women's HospitalC. Laverty (Author/Creator) - Monash UniversityF. Wu (Author/Creator) - Menzies Research InstituteA. Henders (Author/Creator) - QIMR Berghofer Medical Research InstituteJ.J. Ellis (Author/Creator) - QIMR Berghofer Medical Research InstituteI. van der Mei (Author/Creator) - Menzies Research InstituteG.W. Montgomery (Author/Creator) - QIMR Berghofer Medical Research InstituteJ. Blangero (Author/Creator) - The University of Texas Rio Grande ValleyJ.E. Curran (Author/Creator) - The University of Texas Rio Grande ValleyM.P. Johnson (Author/Creator) - The University of Texas Rio Grande ValleyN.G. Martin (Author/Creator) - QIMR Berghofer Medical Research InstituteD.R. Nyholt (Author/Creator) - QIMR Berghofer Medical Research InstituteB.V. Taylor (Author/Creator) - Menzies Research InstituteA.G. Kermode (Author/Creator)
- Publication Details
- Multiple Sclerosis Journal, Vol.22(13), pp.1655-1664
- Publisher
- Sage Publications
- Identifiers
- 991005540255807891
- Copyright
- © 2016 The Author(s).
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
- Additional Information
- Alan Kermode appears as part of the ANZGene Consortium
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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
- Clinical Neurology
- Neurosciences
- ESI research areas
- Neuroscience & Behavior