PMID- 26343388
OWN - NLM
STAT- MEDLINE
DCOM- 20151230
LR  - 20220330
IS  - 1546-1718 (Electronic)
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 47
IP  - 10
DP  - 2015 Oct
TI  - Class II HLA interactions modulate genetic risk for multiple sclerosis.
PG  - 1107-1113
LID - 10.1038/ng.3395 [doi]
AB  - Association studies have greatly refined the understanding of how variation 
      within the human leukocyte antigen (HLA) genes influences risk of multiple 
      sclerosis. However, the extent to which major effects are modulated by 
      interactions is poorly characterized. We analyzed high-density SNP data on 17,465 
      cases and 30,385 controls from 11 cohorts of European ancestry, in combination 
      with imputation of classical HLA alleles, to build a high-resolution map of HLA 
      genetic risk and assess the evidence for interactions involving classical HLA 
      alleles. Among new and previously identified class II risk alleles 
      (HLA-DRB1*15:01, HLA-DRB1*13:03, HLA-DRB1*03:01, HLA-DRB1*08:01 and 
      HLA-DQB1*03:02) and class I protective alleles (HLA-A*02:01, HLA-B*44:02, 
      HLA-B*38:01 and HLA-B*55:01), we find evidence for two interactions involving 
      pairs of class II alleles: HLA-DQA1*01:01-HLA-DRB1*15:01 and 
      HLA-DQB1*03:01-HLA-DQB1*03:02. We find no evidence for interactions between 
      classical HLA alleles and non-HLA risk-associated variants and estimate a minimal 
      effect of polygenic epistasis in modulating major risk alleles.
FAU - Moutsianas, Loukas
AU  - Moutsianas L
AD  - Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
FAU - Jostins, Luke
AU  - Jostins L
AD  - Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
FAU - Beecham, Ashley H
AU  - Beecham AH
AD  - John P. Hussman Institute for Human Genomics, University of Miami, Miller School 
      of Medicine, Miami, Florida, USA.
FAU - Dilthey, Alexander T
AU  - Dilthey AT
AD  - Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
FAU - Xifara, Dionysia K
AU  - Xifara DK
AD  - Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
FAU - Ban, Maria
AU  - Ban M
AD  - Department of Clinical Neurosciences, University of Cambridge, Cambridge 
      Biomedical Campus, Cambridge, UK.
FAU - Shah, Tejas S
AU  - Shah TS
AD  - Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
FAU - Patsopoulos, Nikolaos A
AU  - Patsopoulos NA
AD  - Program in Translational NeuroPsychiatric Genomics, Ann Romney Center for 
      Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, 
      Boston, Massachusetts, USA.
AD  - Department of Medicine, Division of Genetics, Brigham and Women's Hospital, 
      Boston, Massachusetts, USA.
AD  - Harvard Medical School, Boston, Massachusetts, USA.
AD  - Program in Medical and Population Genetics, Broad Institute of Harvard University 
      and MIT, Cambridge, Massachusetts, USA.
FAU - Alfredsson, Lars
AU  - Alfredsson L
AD  - Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, 
      Sweden.
FAU - Anderson, Carl A
AU  - Anderson CA
AD  - Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
FAU - Attfield, Katherine E
AU  - Attfield KE
AD  - Medical Research Council (MRC) Human Immunology Unit, Weatherall Institute of 
      Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
FAU - Baranzini, Sergio E
AU  - Baranzini SE
AD  - Department of Neurology, University of California, San Francisco, Sandler 
      Neurosciences Center, San Francisco, California, USA.
FAU - Barrett, Jeffrey
AU  - Barrett J
AD  - Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK.
FAU - Binder, Thomas M C
AU  - Binder TMC
AD  - HLA Laboratory, Department of Transfusion Medicine, University Medical Center 
      Hamburg-Eppendorf, Hamburg, Germany.
FAU - Booth, David
AU  - Booth D
AD  - Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, 
      Australia.
FAU - Buck, Dorothea
AU  - Buck D
AD  - Department of Neurology, Klinikum Rechts der Isar, Technische Universitat 
      Munchen, Munich, Germany.
FAU - Celius, Elisabeth G
AU  - Celius EG
AD  - Department of Neurology, Oslo University Hospital, Ulleval, Oslo, Norway.
FAU - Cotsapas, Chris
AU  - Cotsapas C
AD  - Program in Medical and Population Genetics, Broad Institute of Harvard University 
      and MIT, Cambridge, Massachusetts, USA.
AD  - Department of Neurology and Immunobiology, Yale University School of Medicine, 
      New Haven, Connecticut, USA.
AD  - Department of Genetics, Yale University School of Medicine, New Haven, 
      Connecticut, USA.
FAU - D'Alfonso, Sandra
AU  - D'Alfonso S
AD  - Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Department of 
      Health Sciences, University of Eastern Piedmont, Novara, Italy.
FAU - Dendrou, Calliope A
AU  - Dendrou CA
AD  - Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular 
      Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
FAU - Donnelly, Peter
AU  - Donnelly P
AD  - Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
FAU - Dubois, Benedicte
AU  - Dubois B
AD  - Department of Neurosciences, Laboratory for Neuroimmunology, KU Leuven, Leuven, 
      Belgium.
FAU - Fontaine, Bertrand
AU  - Fontaine B
AD  - INSERM, Universite Pierre et Marie Curie, CNRS, Assistance Publique-Hopitaux de 
      Paris (AP-HP), Departement des Maladies du Systeme Nerveux and UMRS 1127-7225, 
      Institut Cerveau Moelle Spinal Cord and Brain Institute, Pitie-Salpetriere, 
      Paris, France.
FAU - Fugger, Lars
AU  - Fugger L
AD  - Medical Research Council (MRC) Human Immunology Unit, Weatherall Institute of 
      Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
AD  - Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular 
      Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
FAU - Goris, An
AU  - Goris A
AD  - Department of Neurosciences, Laboratory for Neuroimmunology, KU Leuven, Leuven, 
      Belgium.
FAU - Gourraud, Pierre-Antoine
AU  - Gourraud PA
AD  - Department of Neurology, University of California, San Francisco, Sandler 
      Neurosciences Center, San Francisco, California, USA.
FAU - Graetz, Christiane
AU  - Graetz C
AD  - Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network 
      (rmn2), Johannes Gutenberg University-Medical Center, Mainz, Germany.
FAU - Hemmer, Bernhard
AU  - Hemmer B
AD  - Department of Neurology, Klinikum Rechts der Isar, Technische Universitat 
      Munchen, Munich, Germany.
AD  - Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
AD  - German Competence Network Multiple Sclerosis (KKNMS), Munich, Germany.
FAU - Hillert, Jan
AU  - Hillert J
AD  - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
CN  - International IBD Genetics Consortium (IIBDGC)
FAU - Kockum, Ingrid
AU  - Kockum I
AD  - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
FAU - Leslie, Stephen
AU  - Leslie S
AD  - Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, 
      Melbourne, Victoria, Australia.
AD  - Department of Mathematics and Statistics, University of Melbourne, Parkville, 
      Melbourne, Victoria, Australia.
FAU - Lill, Christina M
AU  - Lill CM
AD  - Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network 
      (rmn2), Johannes Gutenberg University-Medical Center, Mainz, Germany.
AD  - Platform for Genome Analytics, Institutes of Neurogenetics and Integrative and 
      Experimental Genomics, University of Lubeck, Lubeck, Germany.
FAU - Martinelli-Boneschi, Filippo
AU  - Martinelli-Boneschi F
AD  - Laboratory of Genetics of Neurological Complex Disorders, Institute of 
      Experimental Neurology (INSPE), Division of Neuroscience, San Raffaele Scientific 
      Institute, Milan, Italy.
AD  - Department of Neurology, Institute of Experimental Neurology (INSPE), Division of 
      Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
FAU - Oksenberg, Jorge R
AU  - Oksenberg JR
AD  - Department of Neurology, University of California, San Francisco, Sandler 
      Neurosciences Center, San Francisco, California, USA.
FAU - Olsson, Tomas
AU  - Olsson T
AD  - Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
FAU - Oturai, Annette
AU  - Oturai A
AD  - Department of Neurology, Danish Multiple Sclerosis Center, Copenhagen University 
      Hospital, Copenhagen, Denmark.
FAU - Saarela, Janna
AU  - Saarela J
AD  - Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, 
      Finland.
FAU - Sondergaard, Helle Bach
AU  - Sondergaard HB
AD  - Department of Neurology, Danish Multiple Sclerosis Center, Copenhagen University 
      Hospital, Copenhagen, Denmark.
FAU - Spurkland, Anne
AU  - Spurkland A
AD  - Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
FAU - Taylor, Bruce
AU  - Taylor B
AD  - Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, 
      Australia.
FAU - Winkelmann, Juliane
AU  - Winkelmann J
AD  - Department of Neurology, Klinikum Rechts der Isar, Technische Universitat 
      Munchen, Munich, Germany.
AD  - Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
AD  - Institut fur Humangenetik, Technische Universitat Munchen, Munich, Germany.
AD  - Institut fur Humangenetik, Helmholtz Zentrum Munchen, Munich, Germany.
AD  - Department of Neurology and Neurological Sciences, Center for Sleep Sciences and 
      Medicine, Stanford University, Stanford, California, USA.
FAU - Zipp, Frauke
AU  - Zipp F
AD  - Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network 
      (rmn2), Johannes Gutenberg University-Medical Center, Mainz, Germany.
FAU - Haines, Jonathan L
AU  - Haines JL
AD  - Center for Human Genetics Research, Vanderbilt University Medical Center, 
      Nashville, Tennessee, USA.
FAU - Pericak-Vance, Margaret A
AU  - Pericak-Vance MA
AD  - John P. Hussman Institute for Human Genomics, University of Miami, Miller School 
      of Medicine, Miami, Florida, USA.
FAU - Spencer, Chris C A
AU  - Spencer CCA
AD  - Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
FAU - Stewart, Graeme
AU  - Stewart G
AD  - Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, 
      Australia.
FAU - Hafler, David A
AU  - Hafler DA
AD  - Program in Medical and Population Genetics, Broad Institute of Harvard University 
      and MIT, Cambridge, Massachusetts, USA.
AD  - Department of Neurology and Immunobiology, Yale University School of Medicine, 
      New Haven, Connecticut, USA.
AD  - Broad Institute of Harvard University and MIT, Cambridge, Massachusetts, USA.
FAU - Ivinson, Adrian J
AU  - Ivinson AJ
AD  - Harvard NeuroDiscovery Center, Harvard Medical School, Boston, Massachusetts, 
      USA.
FAU - Harbo, Hanne F
AU  - Harbo HF
AD  - Department of Neurology, Oslo University Hospital, Ulleval, Oslo, Norway.
AD  - University of Oslo, Oslo, Norway.
FAU - Hauser, Stephen L
AU  - Hauser SL
AD  - Department of Neurology, University of California, San Francisco, Sandler 
      Neurosciences Center, San Francisco, California, USA.
FAU - De Jager, Philip L
AU  - De Jager PL
AD  - Program in Translational NeuroPsychiatric Genomics, Ann Romney Center for 
      Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital, 
      Boston, Massachusetts, USA.
AD  - Department of Medicine, Division of Genetics, Brigham and Women's Hospital, 
      Boston, Massachusetts, USA.
AD  - Harvard Medical School, Boston, Massachusetts, USA.
AD  - Program in Medical and Population Genetics, Broad Institute of Harvard University 
      and MIT, Cambridge, Massachusetts, USA.
FAU - Compston, Alastair
AU  - Compston A
AD  - Department of Clinical Neurosciences, University of Cambridge, Cambridge 
      Biomedical Campus, Cambridge, UK.
FAU - McCauley, Jacob L
AU  - McCauley JL
AD  - John P. Hussman Institute for Human Genomics, University of Miami, Miller School 
      of Medicine, Miami, Florida, USA.
FAU - Sawcer, Stephen
AU  - Sawcer S
AD  - Department of Clinical Neurosciences, University of Cambridge, Cambridge 
      Biomedical Campus, Cambridge, UK.
FAU - McVean, Gil
AU  - McVean G
AD  - Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
LA  - eng
GR  - R01NS032830/NS/NINDS NIH HHS/United States
GR  - 084702/Z/08/Z/Wellcome Trust/United Kingdom
GR  - R01NS067305/NS/NINDS NIH HHS/United States
GR  - R25 NS070680/NS/NINDS NIH HHS/United States
GR  - R01 NS067305/NS/NINDS NIH HHS/United States
GR  - 100956/Wellcome Trust/United Kingdom
GR  - RC2GM093080/GM/NIGMS NIH HHS/United States
GR  - RC2 GM093080/GM/NIGMS NIH HHS/United States
GR  - 098051/Wellcome Trust/United Kingdom
GR  - NS26799/NS/NINDS NIH HHS/United States
GR  - NS049477/NS/NINDS NIH HHS/United States
GR  - R01 NS026799/NS/NINDS NIH HHS/United States
GR  - G0000934/Medical Research Council/United Kingdom
GR  - 085475/Z/08/Z/Wellcome Trust/United Kingdom
GR  - R01 NS049477/NS/NINDS NIH HHS/United States
GR  - RC2 NS070340/NS/NINDS NIH HHS/United States
GR  - RC2NS070340/NS/NINDS NIH HHS/United States
GR  - 085475/B/08/Z/Wellcome Trust/United Kingdom
GR  - 1UL1RR024975-01/RR/NCRR NIH HHS/United States
GR  - G0700061/MRC_/Medical Research Council/United Kingdom
GR  - UL1 RR024975/RR/NCRR NIH HHS/United States
GR  - R01 NS032830/NS/NINDS NIH HHS/United States
GR  - 068545/Z/02/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150907
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Alleles
MH  - Epistasis, Genetic
MH  - *Genetic Predisposition to Disease
MH  - Histocompatibility Antigens Class II/genetics/*immunology
MH  - Humans
MH  - Multiple Sclerosis/*genetics
MH  - Polymorphism, Single Nucleotide
PMC - PMC4874245
MID - NIHMS782000
EDAT- 2015/09/08 06:00
MHDA- 2015/12/31 06:00
PMCR- 2016/05/20
CRDT- 2015/09/08 06:00
PHST- 2015/01/13 00:00 [received]
PHST- 2015/08/12 00:00 [accepted]
PHST- 2015/09/08 06:00 [entrez]
PHST- 2015/09/08 06:00 [pubmed]
PHST- 2015/12/31 06:00 [medline]
PHST- 2016/05/20 00:00 [pmc-release]
AID - 10.1038/ng.3395 [doi]
PST - ppublish
SO  - Nat Genet. 2015 Oct;47(10):1107-1113. doi: 10.1038/ng.3395. Epub 2015 Sep 7.