Channing Rheumatoid Arthritis (RA) Research

A Multidisciplinary Approach to Understand RA Etiology, Heterogeneity and Pathobiology to Improve Diagnosis, Prognosis and RA Prevention Strategies

Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting more than 1.5 million Americans and millions more worldwide.

RA is also a systemic rheumatic disease with comorbidities, such as coronary heart disease and respiratory disease outcomes that occur more frequently in RA patients than in non-RA populations. In the Nurses’ Health Studies (NHS) cohorts, Channing Division of Network Medicine (CDNM) investigators have established an excess risk of cardiovascular disease and excess respiratory mortality risk in RA populations.

Current Research

CDNM investigators have built a comprehensive research strategy to:

  • Study the epidemiology and outcomes of RA
  • Identify the genetic determinants of RA
  • Identify gene-environment interactions in RA
  • Define key pathobiological mechanisms influencing RA susceptibility and heterogeneity

We apply a multidisciplinary approach to understand RA etiology, heterogeneity, and pathobiology to improve diagnosis and prognosis, and to develop RA prevention strategies.


Early research at Channing demonstrated the negative effects of heavy tobacco smoking on RA risk and a dose-related gene-environment interaction between the HLA-DRB1 shared epitope and smoking on RA risk.

Our research group has led many of the epidemiologic studies of risk factors, including associating female reproductive factors, dietary patterns/quality, air pollution, and obesity with RA risk.

Risk factors

The rheumatic disease research group at CDNM, led by Drs. Elizabeth Karlson and Karen Costenbader, have studied smoking, perinatal/reproductive factors, air pollution, geography, and metabolic/dietary risk factors for RA. Long-term exposure to lung irritants, with cigarette smoking as the dominant environmental risk factor, predisposes individuals to developing RA. Environmental toxins, such as silica dust and cigarette smoke, may trigger RA-related autoimmunity in the lung.

NHS investigators reported higher relative risks of RA in the U.S. Northeast and Mid-West, regions with higher exposure to these environmental factors, including air pollution. NHS provided evidence for higher RA risk in U.S. women who lived closest to major roads (a proxy for traffic pollution).

Reproductive factors identified in RA include a protective effect of longer duration of breastfeeding, while irregular menstrual cycles and menopause increased the risk for future development of RA.

Obesity is also associated with higher RA risk, primarily for early onset RA at ≤ age 55. Adherence to healthy diet recommendations and moderate alcohol intake reduce risk of RA in the NHS cohorts.

In nested case-control analyses, cytokine biomarkers and inflammatory factors were significantly elevated prior to RA onset, even after adjusting for environmental factors.


Biomarkers studies are a crucial aspect of our research, including:

  • Identifying metabolomic markers of RA susceptibility
  • Investigating the effect of circulating biomarkers, such as inflammatory markers, adipokines, and autoantibodies predicting subsequent RA risk
  • Identifying polygenic risk scores for RA susceptibility
  • Performing integrative analysis of multiple risk factors (including diet, environment, genome-wide associations studies [GWAS] and metabolomics)

Study populations

Study populations developed by CDNM investigators include:

  • Incident RA cases validated by chart review in NHS
  • Incident RA cases validated by chart review in the Nurses' Health Study II (NHS II)
  • Nested case-control study in NHS using samples collected prior to RA onset
  • Nested case-control study in NHS II using samples collected prior to RA onset

National and international collaborations

CDNM leads collaborations with groups such as the Swedish EIRA (Epidemiologic Investigations in Rheumatoid Arthritis) and the University of Colorado SERA (Studies of the Epidemiology of RA) research groups.