The purpose of this K01 application is to support a period of didactic training and mentored research for Dr. Yvette Cozier to study the genetic, as well as non-genetic, etiology of sarcoidosis in black women. Dr. Cozier's long term goal is to reduce health disparities. As an Assistant Professor at the Boston University School of Public Health, and an Epidemiologist at the Slone Epidemiology Center working on Black Women's Health Study (BWHS), she will draw on the strengths of both groups: expertise in statistical genetics, a rich database from a large follow-up study of U.S. black women, the expertise to study illness in black women, and clinical knowledge in sarcoidosis. Her mentors have expertise in all of these areas. Dr. Cozier will conduct a study of selected genetic and non-genetic potential risk factors for sarcoidosis, a chronic, granulomatous, systemic disorder, in black women. Black women bear the largest burden of sarcoidosis in the U.S in terms of incidence, and they are more likely than any other group to be younger at diagnosis, experience progressive disease, and die. Little is established about causes of the disease. The proposed study will be conducted within the BWHS, a prospective follow-up of 59,000 U.S. black women. Begun in 1995, the BWHS has collected self-reported data every two years on diagnoses of illness, including sarcoidosis, and on potential risk factors. In addition, the BWHS has collected cheek cell samples from participants, from which DMAis extracted for genetic analyses. Only self-reported cases of sarcoidosis validated by medical record/physician checklist or information from supplementary questionnaires will be included. The validation study, already in progress in collaboration with pulmonologists at the Sarcoidosis Clinic at Boston Medical Center, has been shown to be feasible. Because of effects on immune function, stress-related factors - - frequent experiences of racism and lower neighborhood socioeconomic status - - will be assessed as risk factors for sarcoidosis. Because of the propensity of sarcoidosis to affect women, there will also be a focus on estrogen exposure. Markers of endogenous and exogenous estrogen exposure, such as age at menarche and oral contraceptive use, respectively, will be assessed in relation to the risk of sarcoidosis. We will also assess alleles of genes involved in sex hormone metabolism, including those involved in the synthesis of sex steroids (CYP17, CYP19), and the metabolism and detoxification of estrogen (COMT, CYP1B1, CYP1A1, ESR1), in relation to sarcoidosis risk. The ultimate goal of these projects is to improve understanding of the etiology of sarcoidosis, and to develop Dr. Cozier's capability to independently extend this research.
