Multi-racial genetic analysis of hidradenitis suppurativa

项目摘要 化脓性汗腺炎（HS）是一种未被充分认识的常见免疫介导的皮肤病 以腹股沟、臀部和腋窝的炎性结节、肿胀和窦道为特征 导致身体和精神上的疾病HS严重影响欧洲裔美国人， 少数民族，如非洲裔美国人，亚洲人和拉丁美洲人。HS的治疗很差，只有一个 单一FDA批准的治疗方法可用。治疗方法的缺乏是由于严重缺乏 理解HS发病机制，特别是涉及的遗传途径。在这 在应用方面，我们利用各种创新方法来解决这一重大差距。首先我们表演 在欧洲、非洲裔美国人和亚洲HS病例中进行的全基因组关联研究（GWAS）， 健康对照其次，我们进行跨种族基因组的荟萃分析，以确定共享和 不同的遗传风险因素。第三，我们将进行多种族空间转录组学和蛋白质组学研究， HS皮肤，以阐明细胞-细胞相互作用，并通过荧光素酶进一步鉴定因果GWAS变体 报告基因测定。总之，这些研究将推进我们对遗传结构的了解， HS在不同种族人群中的免疫生物学，并确定可以 治疗靶向。

Project summary Hidradenitis suppurativa (HS) is an underrecognized common, immune-mediated skin disease characterized by inflammatory nodules, abscesses, and sinus tracts in the groin, buttocks, and axillae leading to devasting physical and emotional morbidity. HS significantly affects European Americans and minorities such as African-Americans, Asians, and Latinos. Treatments for HS are poor, with only a single FDA-approved therapy available. The paucity of treatments is driven by a profound lack of understanding of HS pathogenesis, particularly with respect to the genetic pathways involved. In this application, we utilize a variety of innovative approaches to address this significant gap. First, we perform a genome-wide association study (GWAS) in European, African American, and Asian HS cases and healthy controls. Second, we perform trans-ethnic genome wide meta-analysis to identify shared and distinct genetic risk factors. Third, we will perform multi-racial spatial transcriptomics and proteomics of HS skin to elucidate cell-cell interactions, and further identify causal GWAS variants through luciferase reporter assays. Together, these studies will advance our knowledge of the genetic architecture and immunobiology of HS in different racial populations and identify new biologic pathways that can be therapeutically targeted.