Genetic risk of hidradenitis suppurativa in African Americans

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Project Summary Hidradenitis suppurativa (HS) is a chronic, relapsing, and remitting inflammatory disease of the skin, with a prevalence up to 4% of general population. However, the factors that contribute to HS risk are poorly understood, and this lack of mechanistic understanding is a principal barrier to improved treatments for HS. The difference in the risk of HS by ethnicity in the US is striking. Specifically, African Americans have established prevalence and incidence rates that are approximately 3-fold higher than their European American counterparts. Further, African American patients exhibit higher disease severity and the greatest number of co-morbid conditions. Despite these differences, there have been no studies that have provided insight into the contributors to these extreme HS racial disparities. While an inherited germline genetic component to HS risk is indicated by the fact that up to 40% of HS patients report a family history of disease, the majority of the HS genetic studies focused on targeted sequencing of three candidate genes within the gamma-secretase complex, and remarkably, there are no genome- wide association studies reported in HS yet. The overall goal of this project is to define the genetic contributors to HS risk in African Americans. Using genome-wide and candidate gene approach, we will leverage this unique cohort and other existing genetic resources to thoroughly evaluate our hypothesis through the following two Aims. In Aim 1, we will determine whether genetic African ancestry contributes to risk of HS in African Americans; in Aim 2, we will utilize genome-wide and candidate gene approaches to identify genetic variation associated with HS risk in African Americans. Successful completion of this proposal will provide the first insights into the genetic contributions to risk of HS in African Americans, including mechanistic exploration of the genes identified.