Genetic risk of hidradenitis suppurativa in African Americans - 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.
