Genetic risk of hidradenitis suppurativa in African Americans

非裔美国人化脓性汗腺炎的遗传风险

基本信息

批准号：
10703531
负责人：
Indra Adrianto
金额：
$ 15.2万
依托单位：
HENRY FORD HEALTH SYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-01-12 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10703531
关键词：
Abscess Africa African American African American population African ancestry American Architecture Area Autoimmune Basic Science Candidate Disease Gene Chronic Clinic Data Disease Ethnic Origin Europe European Exhibits Family Family history of Funding General Population Genes Genetic Genetic Risk Genetic Variation Genetic study Genome Scan Goals Grant Health system Heritability Hidradenitis Suppurativa Immunologist Incidence Inflammatory Inherited Lead Michigan National Institute of Arthritis and Musculoskeletal and Skin Diseases Pain Pathway Analysis Patients Physicians Population Prevalence Procedures Relapse Reporting Research Research Personnel Risk Severity of illness Sinus Skin Translational Research United States National Institutes of Health Variant admixture mapping cohort comorbidity experience gamma secretase genetic analysis genetic architecture genetic resource genetic variant genome wide association study genome-wide genome-wide analysis improved insight loss of function mutation new therapeutic target racial disparity risk variant skin disorder targeted sequencing therapy development treatment center

项目摘要

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.

项目概要化脓性汗腺炎（HS）是一种慢性、复发性、缓解性炎症性疾病。皮肤病，其患病率高达普通人群的 4%。然而，导致 HS 的因素人们对风险知之甚少，而缺乏机制理解是风险的主要障碍改善 HS 的治疗方法。在美国，不同种族的热射病风险存在显着差异。具体而言，非裔美国人已确定患病率和发病率比欧美同行高出约 3 倍。此外，非洲美国患者表现出更高的疾病严重程度和最多的合并症状况。尽管存在这些差异，但尚无研究深入探讨这些极端的 HS 种族差异的贡献者。虽然遗传了种系遗传多达 40% 的 HS 患者报告有家族史，这一事实表明了 HS 风险的组成部分对于疾病，大多数 HS 遗传学研究集中于三种疾病的靶向测序 γ-分泌酶复合体中的候选基因，并且值得注意的是，没有基因组- HS 中尚未报道广泛的关联研究。该项目的总体目标是定义遗传非洲裔美国人 HS 风险的贡献者。使用全基因组和候选基因方法，我们将利用这个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标。在目标 1 中，我们将确定遗传非洲人是否血统会增加非裔美国人患热射病的风险；在目标 2 中，我们将利用全基因组和候选基因方法识别与非洲 HS 风险相关的遗传变异美国人。该提案的成功完成将提供对遗传的初步见解对非裔美国人热射病风险的贡献，包括基因的机制探索确定。