University of Miami IBD Genetic Research Center: Understanding the Genetic Architecture of IBD in the LatinX Community

迈阿密大学 IBD 基因研究中心：了解拉丁裔社区 IBD 的遗传结构

• 批准号: 10543290
• 负责人: Maria Teresa Abreu
• 金额: $ 53.6万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10543290
• 关键词: ATAC-seq; Admixture; Affect; African American; Age; Age of Onset; Alleles; American; Biological; Black Populations; Caucasians; Cells; Characteristics; Chromatin; Chronic; Clinical; Clinical Trials; Collection; Colon; Communities; Country; County; Crohn' s disease; Data; Databases; Dendritic Cells; Development; Diet; Disease; Economics; Environment; Environmental Exposure; Epigenetic Process; Europe; European; Florida; Functional disorder; Gene Expression; Generations; Genes; Genetic; Genetic Diseases; Genetic Predisposition to Disease; Genetic Research; Genetic Risk; Genetic Structures; Genetic Variation; Genetic study; Genome; Genomic approach; Genomics; Genotype; Goals; Grant; Hispanic; Hispanic Americans; Hispanic Populations; Immigrant; Immigration; Immune; Immune System Diseases; Immune response; Immunologics; Incidence; Individual; Industrialization; Inflammation; Inflammatory Bowel Diseases; Intestines; Knowledge; Latin America; Latin American; Latinx; Linkage Disequilibrium; Location; Malignant Neoplasms; Maps; Measures; Mediating; Medical; Methods; Modification; Mucosal Immune System; Mucositis; Mucous Membrane; National Institute of Diabetes and Digestive and Kidney Diseases; North America; Not Hispanic or Latino; Operative Surgical Procedures; Pathogenesis; Pathogenicity; Pathway interactions; Patients; Pattern; Phagocytes; Pharmaceutical Preparations; Phenotype; Population; Prevention; Property; Publishing; Research; Resolution; Risk; Role; Sentinel; Severities; Susceptibility Gene; Texas; Ulcerative Colitis; Universities; Work; cohort; disability; disease phenotype; gene environment interaction; genetic approach; genetic architecture; genome wide association study; genomic locus; health data; hispanic community; ileum; improved; interest; intergenerational; macrophage; microbiome; multiple omics; neutrophil; novel; recruit; response; risk variant; sample collection; social; social health determinants; transcriptome sequencing; transcriptomics

PROJECT SUMMARY Inflammatory bowel disease (IBD) is a common and devastating immune-mediated disease in which the mucosal immune system abnormally recognizes the intestinal bacterial flora leading to chronic inflammation. Approximately, 1% of the US population is affected. The causes of Crohn's disease (CD) and ulcerative colitis (UC) lie in the interplay between host response genes and a microbiome with pathogenic properties. IBD incidence has leveled off in the developed world and rising in the newly industrialized world. In the US, we are witnessing a rising incidence in immigrants from low-risk parts of the world, particularly Hispanics. This provides an opportunity for discovery of disease pathogenesis towards a goal of prevention and improved therapies. Unfortunately, most genetic studies of IBD, including from the IBDGC, have focused on individuals of European ancestry from North America and Europe. Moreover, most clinical trials of IBD medications include too few Hispanics or Blacks and thus do not represent the totality of the affected population. Our group has a dedicated research interest on IBD in Latin-American immigrants and American-born Hispanic patients. We have published highly-cited studies of the genotype and phenotype of IBD in the Hispanic population of South Florida. We have also described disparities in medication usage and surgical rates. Important for the notion that IBD is caused by a gene-environment interaction, we have found that IBD is occurring faster in the last 20 years in immigrants from Latin-America. We have been very successful in our collection efforts because of our location and our commitment and engagement in the Hispanic community. We have a unique opportunity and obligation to study this disease within the Hispanic population. Miami-Dade County is over 50% Hispanic. The state of Florida has the 3rd largest Hispanic population and the most diverse in terms of countries of origin. We are poised with the support of an IBDGC grant to expand our collection efforts to the broader state of Florida. Genome-wide association studies (GWAS) have facilitated the discovery of previously unrecognized genes and pathways in IBD and provided the opportunity for unbiased exploration of the genomes of patients with IBD. We will explore genetic variation in a large set of US-born and foreign-born Hispanic IBD cases by focusing on targeted genomic, transcriptomic, and epigenetic differences between immigrant and first-generation Hispanic-Americans with IBD. We will edify how genes and environment interact to result in diverse phenotypic manifestations of IBD. Our group has particular expertise and interest in methods to fine-map previously identified risk loci and access the impact of local genetic ancestry on genotype-ancestry interactions in relation to phenotypic characteristics, with the goal of identifying genetic variation of functional significance. Our proposed studies will expand knowledge of disease phenotype and genetic underpinnings in IBD in this growing Hispanic cohort in the hopes of developing prevention and improved treatment approaches. We will use the complementary strengths of the two PIs to catapult discoveries and meet the goals of the NIDDK IBD Genetics Consortium (IBDGC) to expand the collection of Hispanic IBD patients in the US.

项目摘要 炎症性肠病（IBD）是一种常见且毁灭性的免疫介导的疾病，其中 粘膜免疫系统异常识别导致慢性炎症的肠道细菌菌群。 大约有1％的美国人口受到影响。克罗恩病（CD）和溃疡性结肠炎的原因 （UC）位于宿主反应基因与与致病性质的微生物组之间的相互作用。 IBD 发达国家的发病率已经升级，在新工业化的世界中升高。在美国，我们是 目睹来自世界低风险地区的移民，尤其是西班牙裔的移民发病率上升。这提供了 发现疾病发病机理朝着预防和改善疗法的目标的机会。 不幸的是，包括IBDGC在内的大多数IBD遗传研究都集中在欧洲人的个人上 来自北美和欧洲的祖先。此外，大多数IBD药物的临床试验都太少了 西班牙裔或黑人，因此并不代表受影响人群的整体。 我们的小组在拉丁美洲移民和美国出生的IBD方面具有专门的研究兴趣 西班牙裔患者。我们已经发表了有关西班牙裔IBD的基因型和表型的高度引用的研究 南佛罗里达州人口。我们还描述了用药和手术率的差异。重要的 对于IBD是由基因环境相互作用引起的，我们发现IBD的发生速度更快 在过去的20年中，来自拉丁美洲的移民。我们在收集工作方面非常成功 因为我们的位置以及我们在西班牙裔社区的承诺和参与。我们有一个独特的 在西班牙裔人群中研究这种疾病的机会和义务。迈阿密戴德县超过50％ 西班牙裔。佛罗里达州拥有第三大西班牙裔人口，并且在国家方面最多样化 起源。在IBDGC赠款的支持下，我们准备将我们的收集工作扩展到更广泛的国家 佛罗里达州。全基因组关联研究（GWAS）已促进了先前未知的发现 IBD中的基因和途径，为患者的基因组无偏见提供了机会 与IBD。通过 专注于靶向基因组，转录组和表观遗传学差异 与IBD的西班牙裔美国人。我们将建立基因和环境如何相互作用，从而导致多种表型 IBD的表现。我们的小组对以前的方法具有特殊的专业知识和兴趣 确定了风险基因座，并访问局部遗传血统对基因型 - 矫正相互作用的影响 表型特征，目的是确定功能意义的遗传变异。我们的 拟议的研究将扩大IBD中疾病表型和遗传基础的知识 西班牙裔人群希望开发预防和改进的治疗方法。 我们将利用两个PI的互补优势来弹射发现并实现目标 NIDDK IBD遗传联盟（IBDGC）扩大了美国西班牙裔IBD患者的收集。