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。 皮肤病，患病率高达总人口的4%。然而，导致HS的因素 人们对风险知之甚少，这种缺乏机械性的理解是阻碍 改进了HS的治疗方法。在美国，不同种族患HS的风险差异非常显著。 具体地说，非裔美国人的流行率和发病率是 大约是欧美同行的3倍。此外，非洲 美国患者表现出更高的疾病严重性和最多的共病数量 条件。尽管有这些差异，但还没有研究提供对 造成这些极端的HS种族差异的因素。而一个遗传的生殖系基因 高达40%的HS患者报告有家族病史，这表明HS风险的组成部分 疾病，大多数HS基因研究集中在三个有针对性的测序上 伽马分泌酶复合体中的候选基因，值得注意的是，没有基因组- 广泛的关联研究还没有在HS上报道。这个项目的总体目标是定义基因 非裔美国人中HS风险的贡献者。使用全基因组和候选基因方法， 我们将利用这一独特的队列和其他现有的遗传资源来彻底评估 我们的假设通过以下两个目的来实现。在目标1中，我们将确定非洲人的基因 血统导致非裔美国人患HS的风险；在目标2中，我们将利用全基因组和 确定与非洲HS风险相关的遗传变异的候选基因方法 美国人。这项提议的成功完成将提供对基因的第一次洞察 对非裔美国人HS风险的贡献，包括对基因的机械性探索 已确认身份。

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.