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A5367 - Identification of Environmental Exposures Associated with Risk of Sarcoidosis in African Americans
Author Block: A. M. Levin1, Y. Chen1, R. She1, I. Adrianto1, I. Datta1, M. C. Iannuzzi2, C. Montgomery3, J. Li1, B. Rybicki1; 1Public Health Sciences, Henry Ford Health System, Detroit, MI, United States, 2Internal Medicine, Staten Island University Hosp, Staten Island, NY, United States, 3Oklahoma Medical Research Fdn, Oklahoma City, OK, United States.
Rationale: Sarcoidosis is a multi-organ system, granulomatous disease with a complex etiology likely involving both genetic and environmental factors. Despite the established increased risk of sarcoidosis in African Americans, there are few large epidemiologic studies of environmental factors associated with risk in this susceptible population. The objectives of the current study were to identify environmental exposures associated with risk of sarcoidosis in African Americans and those that differ in effect by self-identified race-ethnicity and genetic ancestry.
Methods: The analytic sample comprised of 2,118 African Americans, 1,223 with and 895 without sarcoidosis, was compiled from three separate studies. Across all three, a common set of environmental exposures were assessed by interviewer-administered questionnaire. Hierarchical clustering and multiple correspondence analysis were used to identify and quantify underlying clusters of environmental exposures. Logistic regression was used to evaluate the association of these exposure clusters, as well as the multiple single exposures that comprise them, with risk of sarcoidosis. A comparison sample of 762 European Americans, 388 with and 374 without sarcoidosis, were used to assess heterogeneity in exposure risk by self-reported ethnicity. For African Americans, RFmix (Maples et al. A J Hum Genet 2013) modeled existing genome-wide genotype data to estimate the genome-wide African ancestry percentage for each participant, which were then used to assess the modifying effect of genetic African ancestry on exposure risk.
Results: Analyzing the 51 exposures with the most complete data across studies, seven exposure clusters were identified, five of which were associated with risk. Clusters characterized by smoke and household pet related were associated with a protective effect, while clusters characterized
by exposure to mold, farm/outdoor animals, and heavy metals were associated with increased risk of saroidosis. The heavy metal exposure cluster was associated with the strongest effect and best exemplified by exposure to aluminum (odds ratio [OR] 3.07; 95% confidence interval [CI] 2.09-4.53; p=1.36*10-8). The effect of aluminum exposure also differed by self-reported race-ethnicity (interaction p=6.69*10-5), with European Americans having no significant association with exposure (OR=0.89; 95% CI 0.59-1.35, p=0.598). Within African Americans, this increased risk was associated with increasing African genetic ancestry (interaction p=0.095), consistent with the expected direction based on the self-reported race-ethnicity analyses.
Conclusions: Our findings suggest that African Americans have sarcoidosis environmental exposure risk profiles that differ from European Americans. These differences may underlie the racially disparate incidence rates and may be partially explained by underlying synergistic gene-environment interactions.