PMID- 26819262
OWN - NLM
STAT- MEDLINE
DCOM- 20180119
LR  - 20220311
IS  - 1477-0970 (Electronic)
IS  - 1352-4585 (Linking)
VI  - 22
IP  - 13
DP  - 2016 Nov
TI  - Genetic loci for Epstein-Barr virus nuclear antigen-1 are associated with risk of 
      multiple sclerosis.
PG  - 1655-1664
AB  - 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 (N(eff)) = 5555) and a large MS GWAS (N(eff) = 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 x 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 x 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 x 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.
CI  - (c) The Author(s), 2016.
FAU - Zhou, Yuan
AU  - Zhou Y
AD  - Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, 
      Australia.
FAU - Zhu, Gu
AU  - Zhu G
AD  - Department of Genetics and Computational Biology, QIMR Berghofer Medical Research 
      Institute, Brisbane, QLD, Australia.
FAU - Charlesworth, Jac C
AU  - Charlesworth JC
AD  - Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, 
      Australia.
FAU - Simpson, Steve Jr
AU  - Simpson S Jr
AD  - Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, 
      Australia.
FAU - Rubicz, Rohina
AU  - Rubicz R
AD  - Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 
      Seattle, WA, USA.
FAU - Goring, Harald Hh
AU  - Goring HH
AD  - South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley 
      School of Medicine, Brownsville, TX, USA.
FAU - Patsopoulos, Nikolaos A
AU  - Patsopoulos NA
AD  - 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.
FAU - Laverty, Caroline
AU  - Laverty C
AD  - Monash Antibody Technologies Facility, Monash University, Melbourne, VIC, 
      Australia.
FAU - Wu, Feitong
AU  - Wu F
AD  - Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, 
      Australia.
FAU - Henders, Anjali
AU  - Henders A
AD  - Department of Genetics and Computational Biology, QIMR Berghofer Medical Research 
      Institute, Brisbane, QLD, Australia.
FAU - Ellis, Jonathan J
AU  - Ellis JJ
AD  - Department of Genetics and Computational Biology, QIMR Berghofer Medical Research 
      Institute, Brisbane, QLD, Australia.
FAU - van der Mei, Ingrid
AU  - van der Mei I
AD  - Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, 
      Australia.
FAU - Montgomery, Grant W
AU  - Montgomery GW
AD  - Department of Genetics and Computational Biology, QIMR Berghofer Medical Research 
      Institute, Brisbane, QLD, Australia.
FAU - Blangero, John
AU  - Blangero J
AD  - South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley 
      School of Medicine, Brownsville, TX, USA.
FAU - Curran, Joanne E
AU  - Curran JE
AD  - South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley 
      School of Medicine, Brownsville, TX, USA.
FAU - Johnson, Matthew P
AU  - Johnson MP
AD  - South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley 
      School of Medicine, Brownsville, TX, USA.
FAU - Martin, Nicholas G
AU  - Martin NG
AD  - Department of Genetics and Computational Biology, QIMR Berghofer Medical Research 
      Institute, Brisbane, QLD, Australia.
FAU - Nyholt, Dale R
AU  - Nyholt DR
AD  - 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.
FAU - Taylor, Bruce V
AU  - Taylor BV
AD  - Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, 
      Australia Bruce.Taylor@utas.edu.au.
CN  - ANZgene consortium
LA  - eng
GR  - R01 HL080149/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Meta-Analysis
PT  - Twin Study
DEP - 20160127
PL  - England
TA  - Mult Scler
JT  - Multiple sclerosis (Houndmills, Basingstoke, England)
JID - 9509185
RN  - 0 (Epstein-Barr Virus Nuclear Antigens)
RN  - O5GA75RST7 (EBV-encoded nuclear antigen 1)
SB  - IM
MH  - *Epstein-Barr Virus Nuclear Antigens
MH  - Genetic Loci
MH  - *Genome-Wide Association Study
MH  - Humans
MH  - Multiple Sclerosis/*etiology
MH  - Risk
OTO - NOTNLM
OT  - EBNA-1
OT  - Epstein-Barr virus
OT  - GWAS
OT  - multiple sclerosis
OT  - non-HLA
OT  - polygenic risk
EDAT- 2016/01/29 06:00
MHDA- 2018/01/20 06:00
CRDT- 2016/01/29 06:00
PHST- 2015/07/17 00:00 [received]
PHST- 2015/12/02 00:00 [accepted]
PHST- 2016/01/29 06:00 [pubmed]
PHST- 2018/01/20 06:00 [medline]
PHST- 2016/01/29 06:00 [entrez]
AID - 1352458515626598 [pii]
AID - 10.1177/1352458515626598 [doi]
PST - ppublish
SO  - Mult Scler. 2016 Nov;22(13):1655-1664. doi: 10.1177/1352458515626598. Epub 2016 
      Jan 27.