Association between Residences in U.S. Northern Latitudes and Rheumatoid Arthritis: A Spatial Analysis of the Nurses’ Health Study

BACKGROUND: The etiology of rheumatoid arthritis (RA) remains largely unknown, although epidemiologic studies suggest genetic and environmental factors may play a role. Geographic variation in incident RA has been observed at the regional level. OBJECTIVE: Spatial analyses are a useful tool for confirming existing exposure hypotheses or generating new ones. To further explore the association between location and RA risk, we analyzed individual-level data from U.S. women in the Nurses’ Health Study, a nationwide cohort study. METHODS: Participants included 461 incident RA cases and 9,220 controls with geocoded addresses; participants were followed from 1988 to 2002. We examined spatial variation using addresses at baseline in 1988 and at the time of case diagnosis or the censoring of controls. Generalized additive models (GAMs) were used to predict a continuous risk surface by smoothing on longitude and latitude while adjusting for known risk factors. Permutation tests were conducted to evaluate the overall importance of location and to identify, within the entire study area, those locations of statistically significant risk. RESULTS: A statistically significant area of increased RA risk was identified in the northeast United States (p-value = 0.034). Risk was generally higher at northern latitudes, and it increased slightly when we used the nurses’ 1988 locations compared with those at the time of diagnosis or censoring. Crude and adjusted models produced similar results. CONCLUSIONS: Spatial analyses suggest women living in higher latitudes may be at greater risk for RA. Further, RA risk may be greater for locations that occur earlier in residential histories. These results illustrate the usefulness of GAM methods in generating hypotheses for future investigation and supporting existing hypotheses.