Contributions of familial rheumatoid arthritis or lupus and environmental factors to risk of rheumatoid arthritis in women: a prospective cohort study

Arthritis Care Res (Hoboken). 2014 Oct;66(10):1438-46. doi: 10.1002/acr.22366.


Objective: We assessed the contributions of familial rheumatoid arthritis (RA) or lupus and environmental factors to the risk of RA.

Methods: Among 121,700 women in the Nurses' Health Study, 65,457 provided data on familial RA/lupus. Among these, 493 RA cases (301 seropositive and 192 seronegative) were validated. We estimated hazard ratios (HRs) for RA comparing those with and without familial RA/lupus, adjusting for environmental factors (smoking, alcohol, body mass index [BMI], parity, breastfeeding, menopause, hormone use, early menarche, and menstrual regularity) using Cox proportional hazards models. Population attributable risks (PARs) for RA within this cohort were calculated for familial RA/lupus, smoking, alcohol, BMI, parity, and breastfeeding.

Results: Familial RA/lupus was significantly associated with RA (HR 3.67), seropositive RA (HR 3.90), and seronegative RA (HR 3.95). After adjusting for environmental factors, familial RA/lupus was significantly associated with RA (HR 3.59, 95% confidence interval 2.94-4.37). Smoking >10 pack-years, overweight, BMI, and premenopause status remained significantly associated with RA after adjusting for familial RA/lupus. For RA in this cohort, the PAR for smoking, BMI, alcohol, parity, or breastfeeding collectively was 41%; the PAR due to heredity from familial RA/lupus was 21%.

Conclusion: In this large, prospective cohort, women with familial RA/lupus had a 4-fold increased risk for RA that remained significant after adjusting for environmental factors. A large proportion of RA risk was attributable to environmental factors, even among those with familial RA/lupus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / epidemiology
  • Arthritis, Rheumatoid / genetics*
  • Case-Control Studies
  • Environment*
  • Female
  • Genetic Predisposition to Disease
  • Health Surveys
  • Humans
  • Lupus Erythematosus, Systemic / diagnosis
  • Lupus Erythematosus, Systemic / epidemiology
  • Lupus Erythematosus, Systemic / genetics*
  • Middle Aged
  • Multivariate Analysis
  • Phenotype
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Assessment
  • Risk Factors
  • Sex Factors
  • United States / epidemiology