Multi-racial genetic analysis of hidradenitis suppurativa

项目总结 化脓性汗腺炎(HS)是一种未被充分认识的常见免疫调节皮肤病 以腹股沟、臀部和腋下的炎性结节、脓肿和窦道为特征 导致严重的身体和精神疾病。HS显著影响欧洲裔美国人和 少数民族，如非裔美国人、亚裔和拉丁裔。HS的治疗方法很差，只有一个 提供FDA批准的单一疗法。治疗方法的匮乏是由于严重缺乏 了解HS的发病机制，特别是关于所涉及的遗传途径。在这 作为这一应用的一部分，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、非裔美国人和亚洲HS病例中的全基因组关联研究(GWAS)和 健康对照组。其次，我们执行跨种族基因组范围的荟萃分析，以识别共享和 不同的遗传风险因素。第三，我们将进行多种族空间转录和蛋白质组学研究 HS皮肤，以阐明细胞与细胞之间的相互作用，并通过荧光素酶进一步确定导致GWAs的变异 记者分析说。总之，这些研究将促进我们对遗传结构和 不同种族人群HS的免疫生物学研究并确定新的生物通路 在治疗上有针对性。

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.