PMID- 26291516
OWN - NLM
STAT- MEDLINE
DCOM- 20160802
LR  - 20240215
IS  - 1476-5470 (Electronic)
IS  - 1466-4879 (Print)
IS  - 1466-4879 (Linking)
VI  - 16
IP  - 7
DP  - 2015 Oct
TI  - Genome-wide association study identifies HLA 8.1 ancestral haplotype alleles as 
      major genetic risk factors for myositis phenotypes.
PG  - 470-80
LID - 10.1038/gene.2015.28 [doi]
AB  - Autoimmune muscle diseases (myositis) comprise a group of complex phenotypes 
      influenced by genetic and environmental factors. To identify genetic risk factors 
      in patients of European ancestry, we conducted a genome-wide association study 
      (GWAS) of the major myositis phenotypes in a total of 1710 cases, which included 
      705 adult dermatomyositis, 473 juvenile dermatomyositis, 532 polymyositis and 202 
      adult dermatomyositis, juvenile dermatomyositis or polymyositis patients with 
      anti-histidyl-tRNA synthetase (anti-Jo-1) autoantibodies, and compared them with 
      4724 controls. Single-nucleotide polymorphisms showing strong associations 
      (P<5x10(-8)) in GWAS were identified in the major histocompatibility complex 
      (MHC) region for all myositis phenotypes together, as well as for the four 
      clinical and autoantibody phenotypes studied separately. Imputation and 
      regression analyses found that alleles comprising the human leukocyte antigen 
      (HLA) 8.1 ancestral haplotype (AH8.1) defined essentially all the genetic risk in 
      the phenotypes studied. Although the HLA DRB1*03:01 allele showed slightly 
      stronger associations with adult and juvenile dermatomyositis, and HLA B*08:01 
      with polymyositis and anti-Jo-1 autoantibody-positive myositis, multiple alleles 
      of AH8.1 were required for the full risk effects. Our findings establish that 
      alleles of the AH8.1 comprise the primary genetic risk factors associated with 
      the major myositis phenotypes in geographically diverse Caucasian populations.
FAU - Miller, F W
AU  - Miller FW
AD  - National Institute of Environmental Health Sciences, National Institutes of 
      Health, Bethesda, MD, USA.
FAU - Chen, W
AU  - Chen W
AD  - M.D. Anderson Cancer Center, Houston, TX, USA.
FAU - O'Hanlon, T P
AU  - O'Hanlon TP
AD  - National Institute of Environmental Health Sciences, National Institutes of 
      Health, Bethesda, MD, USA.
FAU - Cooper, R G
AU  - Cooper RG
AD  - MRC/ARUK Institute for Ageing and Chronic Disease, University of Liverpool, UK.
FAU - Vencovsky, J
AU  - Vencovsky J
AD  - Institute of Rheumatology, Charles University, Prague, Czech Republic.
FAU - Rider, L G
AU  - Rider LG
AD  - National Institute of Environmental Health Sciences, National Institutes of 
      Health, Bethesda, MD, USA.
FAU - Danko, K
AU  - Danko K
AD  - 3rd Department of Internal Medicine, Division of Immunology University of 
      Debrecen, Debrecen, Hungary.
FAU - Wedderburn, L R
AU  - Wedderburn LR
AD  - Institute of Child Health, University College London, London, UK.
FAU - Lundberg, I E
AU  - Lundberg IE
AD  - Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, 
      Karolinska Institutet, Stockholm, Sweden.
FAU - Pachman, L M
AU  - Pachman LM
AD  - Department of Pediatric Rheumatology, Feinberg School of Medicine, Northwestern 
      University, Chicago, IL, USA.
FAU - Reed, A M
AU  - Reed AM
AD  - Mayo Clinic, Rochester, MN, USA.
FAU - Ytterberg, S R
AU  - Ytterberg SR
AD  - Mayo Clinic, Rochester, MN, USA.
FAU - Padyukov, L
AU  - Padyukov L
AD  - Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, 
      Karolinska Institutet, Stockholm, Sweden.
FAU - Selva-O'Callaghan, A
AU  - Selva-O'Callaghan A
AD  - Vall d'Hebron General Hospital, Barcelona, Spain.
FAU - Radstake, T R
AU  - Radstake TR
AD  - Department of Rheumatology and Clinical Immunology, Laboratory for Translational 
      Immunology, Utrecht University Medical Center; and Nijmegen Center for Molecular 
      Life Sciences, Nijmegen, The Netherlands.
FAU - Isenberg, D A
AU  - Isenberg DA
AD  - Division of Medicine, University College London, London, UK.
FAU - Chinoy, H
AU  - Chinoy H
AD  - The National Institute for Health Research Manchester Musculoskeletal Biomedical 
      Research Unit, Centre for Musculoskeletal Research, University of Manchester, 
      Manchester, UK.
FAU - Ollier, W E R
AU  - Ollier WE
AD  - Centre for Integrated Genomic Medical Research, Manchester Academic Health 
      Science Centre, University of Manchester, Manchester, UK.
FAU - Scheet, P
AU  - Scheet P
AD  - M.D. Anderson Cancer Center, Houston, TX, USA.
FAU - Peng, B
AU  - Peng B
AD  - M.D. Anderson Cancer Center, Houston, TX, USA.
FAU - Lee, A
AU  - Lee A
AD  - Robert S. Boas Center for Genomics and Human Genetics, Feinstein Institute for 
      Medical Research, Manhasset, NY, USA.
FAU - Byun, J
AU  - Byun J
AD  - Department of Community and Family Medicine, Dartmouth College, Hanover, NH, USA.
FAU - Lamb, J A
AU  - Lamb JA
AD  - Centre for Integrated Genomic Medical Research, Manchester Academic Health 
      Science Centre, University of Manchester, Manchester, UK.
FAU - Gregersen, P K
AU  - Gregersen PK
AD  - Robert S. Boas Center for Genomics and Human Genetics, Feinstein Institute for 
      Medical Research, Manhasset, NY, USA.
FAU - Amos, C I
AU  - Amos CI
AD  - Department of Community and Family Medicine, Dartmouth College, Hanover, NH, USA.
CN  - Myositis Genetics Consortium
LA  - eng
GR  - P30 CA016672/CA/NCI NIH HHS/United States
GR  - Z01 ES101074-06/ImNIH/Intramural NIH HHS/United States
GR  - 18474/VAC_/Versus Arthritis/United Kingdom
GR  - P30 CA023108/CA/NCI NIH HHS/United States
GR  - 18474/ARC_/Arthritis Research UK/United Kingdom
GR  - MR/K006312/1/MRC_/Medical Research Council/United Kingdom
GR  - Z01 ES101074-07/ImNIH/Intramural NIH HHS/United States
GR  - Z01 ES101074-05/ImNIH/Intramural NIH HHS/United States
GR  - Z01ES101074/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150820
PL  - England
TA  - Genes Immun
JT  - Genes and immunity
JID - 100953417
RN  - 0 (Autoantibodies)
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - *Alleles
MH  - Autoantibodies/immunology
MH  - Case-Control Studies
MH  - Dermatomyositis/genetics
MH  - Female
MH  - Genetic Association Studies
MH  - Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - HLA Antigens/*genetics
MH  - Haplotypes
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Myositis/*genetics
MH  - Polymorphism, Single Nucleotide
MH  - Polymyositis/genetics
MH  - Risk Factors
MH  - White People
PMC - PMC4840953
MID - NIHMS749762
COIS- CONFLICT OF INTEREST: The authors have declared that no competing interests 
      exist.
FIR - Denton, Christopher
IR  - Denton C
FIR - Hilton-Jones, David
IR  - Hilton-Jones D
FIR - Kiely, Patrick
IR  - Kiely P
FIR - Plotz, Paul H
IR  - Plotz PH
FIR - Gourley, Mark
IR  - Gourley M
FIR - Varsani, Hemlata
IR  - Varsani H
EDAT- 2015/08/21 06:00
MHDA- 2016/08/03 06:00
PMCR- 2016/04/22
CRDT- 2015/08/21 06:00
PHST- 2015/02/28 00:00 [received]
PHST- 2015/06/15 00:00 [revised]
PHST- 2015/06/18 00:00 [accepted]
PHST- 2015/08/21 06:00 [entrez]
PHST- 2015/08/21 06:00 [pubmed]
PHST- 2016/08/03 06:00 [medline]
PHST- 2016/04/22 00:00 [pmc-release]
AID - gene201528 [pii]
AID - 10.1038/gene.2015.28 [doi]
PST - ppublish
SO  - Genes Immun. 2015 Oct;16(7):470-80. doi: 10.1038/gene.2015.28. Epub 2015 Aug 20.