Multi-racial genetic analysis of hidradenitis suppurativa

化脓性汗腺炎的多种族遗传分析

基本信息

批准号：
10316891
负责人：
Wilson Liao
金额：
$ 80.76万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-16 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10316891
关键词：
Abscess Academia Address Affect African African American American Architecture Asians Atopic Dermatitis Bioinformatics Biological Biological Assay Buttocks Cell Communication Cells Chinese People Clinical Data Collaborations Cytometry DNA Data Data Set Deposition Development Disease Emotional Europe European Exhibits FDA approved Foundations Future Genetic Genetic Risk Genetic study Genotype Grant Hidradenitis Suppurativa Immune Immunobiology Immunologist Individual Inflammatory Inguinal region International Knowledge Latino Lead Link Luciferases Lupus Mediating Meta-Analysis Methods Minority Morbidity - disease rate Nodule North America Outcome Pathogenesis Pathway interactions Patients Phenotype Population Predisposition Prevalence Proteomics Psoriasis Publishing Race Registries Reporter Research Personnel Resources Risk Sampling Sarcoidosis Severities Sinus Skin Suspensions Taiwan Untranslated RNA Variant Work admixture mapping case control cell type cohort comorbidity database of Genotypes and Phenotypes deep sequencing effective therapy genetic analysis genetic architecture genetic risk factor genetic variant genome wide association study genome-wide genomic locus immunopathology innovation insight meetings multi-racial novel novel therapeutics racial difference racial disparity racial population response single-cell RNA sequencing skin barrier skin disorder therapeutic target transcriptome transcriptomics

项目摘要

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.

项目摘要 Hidradenenitis Purpurativa（HS）是一种未识别的常见，免疫介导的皮肤病腹股沟，臀部和腋窝中的炎症结节，脓肿和窦道为特征导致毁灭性的身体和情感发病率。 HS显着影响欧洲人，非裔美国人，亚洲人和拉丁裔等少数民族。 HS治疗很差，只有单次FDA批准的疗法可用。缺乏治疗的贫困驱动了解HS发病机理，特别是在涉及的遗传途径方面。在这个应用程序，我们利用各种创新方法来解决这一重大差距。首先，我们执行全基因组协会研究（GWAS）在欧洲，非裔美国人和亚洲HS案件中以及健康控制。其次，我们执行跨种族基因组广泛的荟萃分析，以识别共享和独特的遗传危险因素。第三，我们将执行多种族空间转录组学和蛋白质组学 HS皮肤以阐明细胞 - 细胞相互作用，并通过荧光素酶进一步识别因果GWAS变体记者测定法。这些研究将共同提高我们对遗传结构的了解和 HS在不同种族种群中的免疫生物学，并确定可以是的新生物学途径治疗目标。