Evidence map›Paper›PMID 24385024›Full record

SynthesisGenes and immunity2014

The influence of polygenic risk scores on heritability of anti-CCP level in RA.

J Cui, K E Taylor, Y C Lee, H Källberg, M E Weinblatt, J S Coblyn, L Klareskog, L A Criswell, P K Gregersen, N A Shadick and 2 more

Open access · greenAbstract readMeta-AnalysisObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Genes and immunity, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.

  1. Pooled it
  2. Frontiers in immunology · 2018
    Article
  3. Article
  4. Article
  5. Recent Advances in Defining the Genetic Basis of Rheumatoid Arthritis.Annual review of genomics and human genetics · 2016
    Review
  6. Review
  7. Review
  8. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 2 countries.

J CuiDivision of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
K E TaylorRosalind Russell Medical Research Center for Arthritis, Division of Rheumatology, Department of Medicine, University of California, San Francisco, CA, USA.
Y C LeeDivision of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
H KällbergInstitute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
M E WeinblattDivision of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
J S CoblynDivision of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
L KlareskogInstitute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
L A CriswellRosalind Russell Medical Research Center for Arthritis, Division of Rheumatology, Department of Medicine, University of California, San Francisco, CA, USA.
P K GregersenThe Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhasset, NY, USA.
N A ShadickDivision of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
R M Plenge1] 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.
E W KarlsonDivision of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Brigham and Women's Hospital · USHarvard University · USKarolinska Institutet · SEFeinstein Institute for Medical Research · USUniversity of California, San Francisco · US

Funding

Genetic predictors of response to anti-TNF therapy in rheumatoid arthritisU01GM092691 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI BRENNER, MICHAEL B., RAYCHAUDHURI, SOUMYA · 2010 to 2014
$7.5M
European Research Council 250167NIGMS NIH HHS U01 GM092691
6 · The paper itself

Abstract

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 × 10(-11) for rs1980493. There were 112 SNPs in this region that exceeded the genome-wide significance threshold of 5 × 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 × 10(-7). None of the known RA risk alleles (∼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.

Indexed as

Arthritis, RheumatoidAutoantibodiesCase-Control StudiesCohort StudiesFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGPI-Linked ProteinsHLA-DR3 AntigenHLA-DRB1 ChainsHumansLinkage DisequilibriumMaleMiddle AgedModels, GeneticPeptides, CyclicAutoantibodiescyclic citrullinated peptideGP2 protein, humanGPI-Linked ProteinsHLA-DR3 AntigenHLA-DRB1 ChainsPeptides, Cyclic

Identifiers

PMID24385024
PMCPMC3948067
OpenAlexW2033800025

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.