Genetic risk of hidradenitis suppurativa in African Americans

非裔美国人化脓性汗腺炎的遗传风险

• 批准号: 10549738
• 负责人: Indra Adrianto
• 金额: $ 16.72万
• 依托单位: HENRY FORD HEALTH SYSTEM
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-12 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10549738
• 关键词: Abscess; Acceleration; Africa; African American; African American population; African ancestry; American; Architecture; Area; Autoimmune; Basic Science; Candidate Disease Gene; Chronic; Clinic; Data; Disease; Disease remission; 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 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

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.

项目摘要 Hidradenenitis Purpurativa（HS）是一种慢性，复发的，使炎症性疾病的疾病 皮肤，占普通人群的4％。但是，导致HS的因素 风险知之甚少，缺乏机械理解是 改进了HS的治疗方法。美国族裔风险的差异令人震惊。 具体而言，非洲裔美国人已经确立了患病率和发病率 比其欧美对手高约3倍。此外，非洲 美国患者表现出较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，但尚无研究的洞察力 这些极端HS种族差异的原因。而遗传的种系遗传 HS风险的组成部分表明，高达40％的HS患者报告了家族病史。 疾病，大多数HS遗传研究都集中在三个靶向测序上 γ-分泌酶复合物中的候选基因，而且没有基因组 - HS报告的广泛关联研究。该项目的总体目标是定义遗传 非裔美国人HS风险的贡献者。使用全基因组和候选基因方法， 我们将利用这种独特的队列和其他现有的遗传资源来彻底评估 我们通过以下两个目标的假设。在AIM 1中，我们将确定遗传非洲是否 祖先有助于非洲裔美国人的HS风险；在AIM 2中，我们将利用全基因组和 候选基因方法鉴定与非洲HS风险相关的遗传变异 美国人。该提案的成功完成将为遗传提供首次见解 非洲裔美国人的HS风险的贡献，包括对基因的机械探索 确定。