Evidence map›Paper›PMID 41548231›Full record

ArticleRheumatology (Oxford, England)2026

Heterogeneity in the association of genetic risk for RA and resultant RA phenotypes.

Thomas R Riley, Austin M Wheeler, Bryant R England, Grant W Cannon, Brian Sauer, Gary A Kunkel, Katherine D Wysham, Beth I Wallace, Paul A Monach, Andreas Reimold and 11 more

Abstract read
In one paragraph

Article in Rheumatology (Oxford, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

21 authors.

Thomas R RileyUniversity of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0009-0003-0194-7562
Austin M WheelerVA Nebraska-Western Iowa Health Care System, Omaha, NE, USA.ORCID 0000-0002-8816-7782
Bryant R EnglandVA Nebraska-Western Iowa Health Care System, Omaha, NE, USA.ORCID 0000-0002-9649-3588
Grant W CannonVA Salt Lake City & University of Utah, Salt Lake City, UT, USA.ORCID 0000-0001-6640-9173
Brian SauerVA Salt Lake City & University of Utah, Salt Lake City, UT, USA.
Gary A KunkelVA Salt Lake City & University of Utah, Salt Lake City, UT, USA.
Katherine D WyshamVA Puget Sound Health Care System & University of Washington, Seattle, WA, USA.ORCID 0000-0001-8707-7649
Beth I WallaceVA Ann Arbor Healthcare System, Ann Arbor, MI, USA.ORCID 0000-0003-1802-1427
Paul A MonachVA Boston Healthcare System & Harvard Medical School, Boston, MA, USA.
Andreas ReimoldDallas VA Health System & University of Texas Southwestern, Dallas, TX, USA.
Gail S KerrWashington, DC VA, Georgetown University, & Howard University, Washington, DC, USA.
Isaac D SmithDurham VA Medical Center & Duke University, Durham, NC, USA.
John Steuart RichardsVA Pittsburgh Healthcare System & University of Pittsburgh, PA, USA.
Iris LeeVA St Louis Health Care & Washington University in St Louis, St Louis, USA.ORCID 0000-0002-6064-2158
Geoffrey M ThieleVA Nebraska-Western Iowa Health Care System, Omaha, NE, USA.
Rui XiaoUniversity of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0000-0002-2727-8171
Scott M DamrauerUniversity of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
Michael G LevinUniversity of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
Michael D GeorgeUniversity of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.ORCID 0000-0002-0398-2308
Ted R MikulsVA Nebraska-Western Iowa Health Care System, Omaha, NE, USA.
Joshua F BakerUniversity of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.

Funding

Tracking and Evaluation CoreU54GM115458 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI RIZZO, MATTHEW · 2016 to 2025
$42.8M
Research Project 3U54MD012530 · NIMHD · DUKE UNIVERSITY · PI JOHNSON, KIMBERLY S. · 2017 to 2022
$8.8M
Clinical Pharmacoepidemiology Training ProgramT32GM075766 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI Sean Hennessy, Charles Edward Leonard · 2006 to 2026
$8.4M
ARTHFNBLRD VA I01 BX003635BLRD VA IK2 BX006551CSRD VA I01 CX001703CSRD VA IK2 CX002203CSRD VA IK2 CX002351CSRD VA IK2 CX002430Doris Duke Foundation 2023-0224Duke Center for Research to Advance Healthcare Equity # 3U54MD012530-05S2National Institutes of Health Pharmacoepidemiology T32 5T32GM075766-17NIGMS NIH HHS T32 GM075766NIGMS NIH HHS U54 GM115458NIMHD NIH HHS U54 MD012530Rehabilitation Research & Development Merit RX003644Rehabilitation Research & Development Merit RX004770Rheumatology Research FoundationRRD VA I01 RX003644RRD VA I01 RX004770US Department of Defence PR200793US Department of Veterans Affairs IK2-BX006551VA BLRD BX003635VA CSR&D CX002203VA CSR&D CX002351VA CSR&D CX002430
6 · The paper itself

Abstract

objectivesThe impact of the genetic risk for RA on resultant disease phenotype in RA is incompletely understood. Using individual genetic variants associated with RA and a polygenic score (PGS), we hypothesized that those with higher genetic risk for RA would demonstrate a more severe disease course.

methodsWe genotyped participants from the Veterans Affairs RA registry (VARA), a prospective cohort of RA. We evaluated associations between PTPN22 R620W genotype, HLA-DRB1 shared epitope (SE; 0, 1, or 2 copies of a high-risk HLA allele), and a non-HLA PGS with RA disease activity scores and disease characteristics using linear and logistic regression, adjusted for sex, age, and principal components of population structure.

resultsAmong 2557 VARA participants, 50 (2%) were homozygous for PTPN22 R620W, and 1603 (62%) had a PGS greater than the 50th percentile when compared with a reference population. PTPN22 R620W, SE, and the PGS were strongly associated with seropositivity (PGS OR = 1.41, 95% CI 1.26-1.58, P < 0.001). At enrolment, compared with those with no R620W alleles, those with two alleles had higher disease activity [CDAI β = 6.10, 95% CI 1.23-10.97, P = 0.014]; no difference was observed for those with one R620W allele or SE. PGS was not significantly associated with disease activity.

conclusionGenetic variation renders heterogeneous associations with disease activity and phenotype in RA. Individual genetic variants and pathway-specific genetic risk associated with RA may be more informative than the pooled genetic risk in understanding disease phenotype and disease activity.

Indexed as

Arthritis, RheumatoidGenetic Predisposition to DiseaseHLA-DRB1 ChainsProtein Tyrosine Phosphatase, Non-Receptor Type 22AgedFemaleGenetic Risk ScoreGenotypeHumansMaleMiddle AgedPhenotypeProspective StudiesRegistriesSeverity of Illness IndexHLA-DRB1 ChainsProtein Tyrosine Phosphatase, Non-Receptor Type 22PTPN22 protein, humandisease activity scoregeneticsphenotypepolygenic scorePTPN22RA

Identifiers

PMID41548231
PMCPMC13078286

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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.