Genetic risk of hidradenitis suppurativa in African Americans

项目摘要 化脓性汗腺炎（HS）是一种慢性、复发性和缓解性炎症性疾病， 皮肤，患病率高达4%的一般人口。然而，导致HS的因素 风险知之甚少，这种缺乏机械性的理解是一个主要障碍， 改善HS治疗。在美国，不同种族的HS风险差异惊人。 具体来说，非裔美国人已经确定了患病率和发病率， 比美国同行高出约3倍。此外，非洲 美国患者表现出更高的疾病严重程度和最大数量的共病 条件尽管存在这些差异，但还没有研究提供了对 造成HS种族差异的罪魁祸首虽然遗传的生殖系基因 高达40%的HS患者报告有家族史，这一事实表明， 大多数HS基因研究集中在三个基因的靶向测序上， γ-分泌酶复合体中的候选基因，值得注意的是，没有基因组- 广泛的关联研究报告在HS尚未。该项目的总体目标是确定遗传 非裔美国人HS风险的贡献者。利用全基因组和候选基因方法， 我们将利用这一独特的群体和其他现有的遗传资源， 我们的假设通过以下两个目的。在目标1中，我们将确定遗传非洲人是否 血统有助于非裔美国人HS的风险;在目标2中，我们将利用全基因组和 用候选基因方法鉴定与非洲HS风险相关的遗传变异 美国人成功完成这一提案将提供第一次深入了解遗传 非裔美国人HS风险的贡献，包括基因的机械探索 鉴定

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.