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| PMID |
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| TITLE |
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| 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 |
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| HISTORY |
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| 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 |
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| INVESTIGATORS |
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| JOURNAL |
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| 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 |
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| MEDLINE JOURNAL |
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| MEDLINETA: Mult Scler |
| COUNTRY: England |
| ISSNLINKING: 1352-4585 |
| NLMUNIQUEID: 9509185 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| JOURNAL ARTICLE |
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| COMMENTS AND CORRECTIONS |
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| GRANTS |
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| GENERAL NOTE |
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| KEYWORDS |
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| KEYWORD |
| EBNA-1 |
| Epstein-Barr virus |
| GWAS |
| multiple sclerosis |
| non-HLA |
| polygenic risk |
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| MESH HEADINGS |
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| SUPPLEMENTARY MESH |
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| GENE SYMBOLS |
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| CHEMICALS |
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