Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
26819262
TITLE
Genetic loci for Epstein-Barr virus nuclear antigen-1 are associated with risk of multiple sclerosis.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
Infection with the Epstein-Barr virus (EBV) is associated with an increased risk of multiple sclerosis (MS).
OBJECTIVE NlmCategory: 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 NlmCategory: 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 NlmCategory: 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 NlmCategory: 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.
The Author(s), 2016.
DATE PUBLISHED
2016 Jan 27
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2016/01/29 06:00
pubmed 2016/01/29 06:00
medline 2016/01/29 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Zhou Y Zhou Yuan Y Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
Zhu G Zhu Gu G Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Charlesworth JC Charlesworth Jac C JC Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
Simpson S Jr Simpson Steve S Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
Rubicz R Rubicz Rohina R Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Göring HH Göring Harald Hh HH South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
Patsopoulos NA Patsopoulos Nikolaos A NA Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA/Harvard Medical School, Boston, MA, USA/Broad Institute, Cambridge, MA, USA.
Laverty C Laverty Caroline C Monash Antibody Technologies Facility, Monash University, Melbourne, VIC, Australia.
Wu F Wu Feitong F Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
Henders A Henders Anjali A Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Ellis JJ Ellis Jonathan J JJ Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
van der Mei I van der Mei Ingrid I Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia.
Montgomery GW Montgomery Grant W GW Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Blangero J Blangero John J South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
Curran JE Curran Joanne E JE South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
Johnson MP Johnson Matthew P MP South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
Martin NG Martin Nicholas G NG Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Nyholt DR Nyholt Dale R DR Statistical and Genomic Epidemiology Laboratory, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia/Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Taylor BV Taylor Bruce V BV Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia Bruce.Taylor@utas.edu.au.
ANZgene consortium
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Multiple sclerosis (Houndmills, Basingstoke, England)
ISOABBREVIATION: Mult. Scler.
YEAR: 2016
MONTH: Jan
DAY: 27
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1477-0970
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Mult Scler
COUNTRY: England
ISSNLINKING: 1352-4585
NLMUNIQUEID: 9509185
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
JOURNAL ARTICLE
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
KEYWORD
EBNA-1
Epstein-Barr virus
GWAS
multiple sclerosis
non-HLA
polygenic risk
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's