Identification of Environmental Exposures Associated with Risk of Sarcoidosis in African Americans
Levin AM, She R, Chen Y, Adrianto I, Datta I, Loveless IM, Garman L, Montgomery CG, Li J, Iannuzzi M, and Rybicki BA. Identification of Environmental Exposures Associated with Risk of Sarcoidosis in African Americans. Ann Am Thorac Soc 2023.
Ann Am Thorac Soc
RATIONALE: Sarcoidosis is a racially disparate, granulomatous disease likely due to environmental exposures, genes, and their interactions. Despite increased risk in African Americans (AAs), few environmental risk factor studies in this susceptible population exist.
OBJECTIVES: To identify environmental exposures associated with risk of sarcoidosis in AAs and those that differ in effect by self-identified race and genetic ancestry.
METHODS: The study sample comprised 2,096 AAs (1,205 with and 891 without sarcoidosis), compiled from three component studies. Unsupervised clustering and multiple correspondence analyses were used to identify underlying clusters of environmental exposures. Mixed effects logistic regression was used to evaluate the association of these exposure clusters and the 51 single component exposures with risk of sarcoidosis. A comparison case-control sample of 762 European Americans (EAs, 388 with and 374 without sarcoidosis) was used to assess heterogeneity in exposure risk by race.
MEASUREMENT AND MAIN RESULTS: Seven exposure clusters were identified, five of which were associated with risk. The exposure cluster with the strongest risk association was comprised of metals (p<0.001), and within this cluster, exposure to aluminum had the highest risk (OR 3.30; 95%CI 2.23-4.09; p<0.001). This effect also differed by race (p<0.001), with EAs having no significant association with exposure (OR=0.86; 95% CI 0.56-1.33). Within AAs, increased risk was dependent upon genetic African ancestry (p=0.047).
CONCLUSIONS: Our findings support AAs having sarcoidosis environmental exposure risk profiles that differ from EAs. These differences may underlie racially disparate incidence rates, partially explained by genetic variation differing by African ancestry.
ePub ahead of print