Evidence map›Paper›PMID 39919896›Full record

ArticleAnnals of the rheumatic diseases2025

Uncovering specific genetic-respiratory disease endotypes for rheumatoid arthritis risk.

Vanessa L Kronzer, Katrina A Williamson, Keigo Hayashi, Elizabeth J Atkinson, Cynthia S Crowson, Xiaosong Wang, Jing Cui, James R Cerhan, Jennifer A Sletten, Gregory C McDermott and 4 more

Abstract read
In one paragraph

Article in Annals of the rheumatic diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Review
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

14 authors.

Vanessa L KronzerMayo Clinic, Rochester, NY, USA. Electronic address: kronzer.vanessa@mayo.edu.
Katrina A WilliamsonMayo Clinic, Rochester, NY, USA.
Keigo HayashiHarvard Medical School, Boston, Massachusetts, USA.
Elizabeth J AtkinsonDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, NY, USA.
Cynthia S CrowsonMayo Clinic, Rochester, NY, USA; Department of Quantitative Health Sciences, Mayo Clinic, Rochester, NY, USA.
Xiaosong WangDivision of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Jing CuiDepartment of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
James R CerhanDepartment of Quantitative Health Sciences, Mayo Clinic, Rochester, NY, USA.
Jennifer A SlettenMayo Clinic, Rochester, NY, USA.
Gregory C McDermottHarvard Medical School, Boston, Massachusetts, USA. Electronic address: https://twitter.com/gregmcdermott.
Elena K JoernsMayo Clinic, Rochester, NY, USA.
Robert VassalloMayo Clinic, Rochester, NY, USA.
John M DavisMayo Clinic, Rochester, NY, USA. Electronic address: https://twitter.com/johndavis.
Jeffrey A SparksHarvard Medical School, Boston, Massachusetts, USA. Electronic address: https://twitter.com/jeffsparks.

Funding

HEART DISEASE IN RHEUMATOID ARTHRITISR01AR046849 · NIAMS · MAYO CLINIC ROCHESTER · PI CROWSON, CYNTHIA S · 2000 to 2022
$11.3M
VERITY: Value and Evidence in Rheumatology using bioInformaTics, and advanced analYticsP30AR072577 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Daniel Hal Solomon · 2017 to 2026
$9.8M
Joint Biology Consortium Resource-based CenterP30AR070253 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Peter A Nigrovic, Jeffrey Andrew Sparks · 2016 to 2026
$9.4M
Rheumatoid Arthritis-Related Autoantibodies, Articular Inflammation, and RA-Associated Interstitial Lung DiseaseR01AR077607 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI SPARKS, JEFFREY ANDREW · 2021 to 2025
$3.7M
Rheumatoid Arthritis-associated Parenchymal Lung Disease: Clinical and Molecular PhenotypesR01HL155522 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI Jeffrey Andrew Sparks, George R Washko · 2022 to 2026
$3.5M
Immunologic and Clinical Sequelae after COVID-19 in Patients with Systemic Autoimmune Rheumatic DiseasesR01AR080659 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Jeffrey Andrew Sparks · 2023 to 2026
$2.9M
NHLBI NIH HHS R01 HL155522NIAMS NIH HHS P30 AR070253NIAMS NIH HHS P30 AR072577NIAMS NIH HHS R01 AR046849NIAMS NIH HHS R01 AR077607NIAMS NIH HHS R01 AR080659
6 · The paper itself

Abstract

objectiveWe aimed to identify specific genetic-respiratory disease endotypes for rheumatoid arthritis (RA) risk.

methodsThis case-control study used the Mass General Brigham (MGB) and Mayo Clinic (MC) Biobanks for discovery and replication, respectively. We matched criteria-confirmed incident RA cases to four non-RA controls on age, sex and health record history. Genetic exposures included the top 11 RA risk alleles, and a validated human leucocyte antigen (HLA) genetic risk score (GRS). We identified seven respiratory diseases by codes. Using logistic regression models adjusting for potential confounders, we estimated Rs with 95% CIs for the interactions between genetic and respiratory exposures for RA risk.

resultsWe identified 653 RA cases and 2607 controls in MGB, and 428 incident RA cases and 1712 non-RA controls in MC (mean age 64, 69% female). Respiratory diseases were associated with an increased risk of RA (OR 1.34, 95% CI 1.05, 1.71). Six out of 11 non-HLA RA risk alleles interacted strongly with specific respiratory diseases for RA risk, including NFKBIE and sinusitis (OR 5.49, 95% CI 1.56, 19.4 MGB; 5.26, 95% CI 2.00, 13.86 MC) and FAM167A and acute sinusitis for seronegative RA (OR 6.00, 95% CI 2.09, 17.24 MGB; 4.90, 95% CI 1.71, 14.1 MC). The RA HLA GRS interacted synergistically with interstitial lung disease for RA risk (OR 5.41, 95% CI 2.71, 10.8 in MC), with DPB1*02:01, DRB1*16:01 and DRB1*04:04 best predicting RA (positive predictive value 61%).

conclusionSeveral genetic-respiratory disease interactions strongly drive RA onset. If confirmed, these novel associations may reflect RA endotypes that can facilitate individualised prevention, diagnosis and treatment.

Indexed as

Arthritis, RheumatoidRespiratory Tract DiseasesAgedAllelesCase-Control StudiesFemaleGenetic Predisposition to DiseaseHumansMaleMiddle AgedRisk FactorsEpidemiologyGeneticPolymorphismPulmonary FibrosisRheumatoid Arthritis

Identifiers

PMID39919896
PMCPMC11822224

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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.