PMID- 24385024
OWN - NLM
STAT- MEDLINE
DCOM- 20141118
LR  - 20220129
IS  - 1476-5470 (Electronic)
IS  - 1466-4879 (Print)
IS  - 1466-4879 (Linking)
VI  - 15
IP  - 2
DP  - 2014 Mar
TI  - The influence of polygenic risk scores on heritability of anti-CCP level in RA.
PG  - 107-14
LID - 10.1038/gene.2013.68 [doi]
AB  - The objective of this study was to study genetic factors that influence 
      quantitative anticyclic citrullinated peptide (anti-CCP) antibody levels in RA 
      patients. We carried out a genome-wide association study (GWAS) meta-analysis 
      using 1975 anti-CCP+ RA patients from three large cohorts, the Brigham Rheumatoid 
      Arthritis Sequential Study (BRASS), North American Rheumatoid Arthritis 
      Consortium (NARAC) and the Epidemiological Investigation of RA (EIRA). We also 
      carried out a genome-wide complex trait analysis (GCTA) to estimate the 
      heritability of anti-CCP levels. GWAS-meta-analysis showed that anti-CCP levels 
      were most strongly associated with the human leukocyte antigen (HLA) region with 
      a P-value of 2 x 10(-11) for rs1980493. There were 112 SNPs in this region that 
      exceeded the genome-wide significance threshold of 5 x 10(-8), and all were in 
      linkage disequilibrium (LD) with the HLA- DRB1*03 allele with LD r(2) in the 
      range of 0.25-0.88. Suggestive novel associations outside of the HLA region were 
      also observed for rs8063248 (near the GP2 gene) with a P-value of 3 x 10(-7). 
      None of the known RA risk alleles ( approximately 52 loci) were associated with anti-CCP level. 
      Heritability analysis estimated that 44% of anti-CCP variation was attributable 
      to genetic factors captured by GWAS variants. In summary, anti-CCP level is a 
      heritable trait, and HLA-DR3 and GP2 are associated with lower anti-CCP levels.
FAU - Cui, J
AU  - Cui J
AD  - Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 
      Harvard Medical School, Boston, MA, USA.
FAU - Taylor, K E
AU  - Taylor KE
AD  - Rosalind Russell Medical Research Center for Arthritis, Division of Rheumatology, 
      Department of Medicine, University of California, San Francisco, CA, USA.
FAU - Lee, Y C
AU  - Lee YC
AD  - Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 
      Harvard Medical School, Boston, MA, USA.
FAU - Kallberg, H
AU  - Kallberg H
AD  - Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
FAU - Weinblatt, M E
AU  - Weinblatt ME
AD  - Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 
      Harvard Medical School, Boston, MA, USA.
FAU - Coblyn, J S
AU  - Coblyn JS
AD  - Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 
      Harvard Medical School, Boston, MA, USA.
FAU - Klareskog, L
AU  - Klareskog L
AD  - Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
FAU - Criswell, L A
AU  - Criswell LA
AD  - Rosalind Russell Medical Research Center for Arthritis, Division of Rheumatology, 
      Department of Medicine, University of California, San Francisco, CA, USA.
FAU - Gregersen, P K
AU  - Gregersen PK
AD  - The Feinstein Institute for Medical Research, North Shore-Long Island Jewish 
      Health System, Manhasset, NY, USA.
FAU - Shadick, N A
AU  - Shadick NA
AD  - Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 
      Harvard Medical School, Boston, MA, USA.
FAU - Plenge, R M
AU  - Plenge RM
AD  - 1] Division of Rheumatology, Immunology and Allergy, Brigham and Women's 
      Hospital, Harvard Medical School, Boston, MA, USA [2] Division of Genetics, 
      Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [3] Medical 
      and Population Genetics Program, Chemical Biology Program, Broad Institute, 
      Cambridge, MA, USA.
FAU - Karlson, E W
AU  - Karlson EW
AD  - Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 
      Harvard Medical School, Boston, MA, USA.
LA  - eng
GR  - 250167/ERC_/European Research Council/International
GR  - U01 GM092691/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Meta-Analysis
PT  - Observational Study
DEP - 20140102
PL  - England
TA  - Genes Immun
JT  - Genes and immunity
JID - 100953417
RN  - 0 (Autoantibodies)
RN  - 0 (GP2 protein, human)
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (HLA-DR3 Antigen)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (Peptides, Cyclic)
RN  - 0 (cyclic citrullinated peptide)
SB  - IM
MH  - Arthritis, Rheumatoid/*genetics/*immunology
MH  - Autoantibodies/*immunology
MH  - Case-Control Studies
MH  - Cohort Studies
MH  - Female
MH  - GPI-Linked Proteins/genetics
MH  - Genetic Predisposition to Disease
MH  - Genome-Wide Association Study
MH  - HLA-DR3 Antigen/genetics/immunology
MH  - HLA-DRB1 Chains/genetics/immunology
MH  - Humans
MH  - Linkage Disequilibrium
MH  - Male
MH  - Middle Aged
MH  - Models, Genetic
MH  - Peptides, Cyclic/*immunology
MH  - Polymorphism, Single Nucleotide
MH  - Prospective Studies
PMC - PMC3948067
MID - EMS56063
OID - NLM: EMS56063
EDAT- 2014/01/05 06:00
MHDA- 2014/11/19 06:00
PMCR- 2014/09/01
CRDT- 2014/01/04 06:00
PHST- 2013/08/28 00:00 [received]
PHST- 2013/11/18 00:00 [revised]
PHST- 2013/11/19 00:00 [accepted]
PHST- 2014/01/04 06:00 [entrez]
PHST- 2014/01/05 06:00 [pubmed]
PHST- 2014/11/19 06:00 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - gene201368 [pii]
AID - 10.1038/gene.2013.68 [doi]
PST - ppublish
SO  - Genes Immun. 2014 Mar;15(2):107-14. doi: 10.1038/gene.2013.68. Epub 2014 Jan 2.