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.

项目概要 炎症性肠病（IBD）是一种常见且具有破坏性的免疫介导疾病，其中 粘膜免疫系统异常识别肠道菌群，导致慢性炎症。 大约 1% 的美国人口受到影响。克罗恩病 (CD) 和溃疡性结肠炎的病因 （UC）在于宿主反应基因和具有致病特性的微生物组之间的相互作用。炎症性肠病 发达国家的发病率已趋于平稳，而新兴工业化国家的发病率则呈上升趋势。在美国，我们是 来自世界低风险地区的移民，尤其是西班牙裔移民的发病率不断上升。这提供了 为实现预防和改进治疗目标而发现疾病发病机制的机会。 不幸的是，大多数 IBD 基因研究，包括来自 IBDGC 的研究，都集中在欧洲人的个体上。 血统来自北美和欧洲。此外，大多数 IBD 药物的临床试验涉及的数据太少。 因此，西班牙裔或黑人并不代表受影响人口的全部。 我们小组对拉丁美洲移民和美国出生的 IBD 有专门的研究兴趣 西班牙裔患者。我们发表了关于西班牙裔 IBD 基因型和表型的高被引研究 南佛罗里达州的人口。我们还描述了药物使用和手术率的差异。重要的 对于 IBD 是由基因与环境相互作用引起的观点，我们发现 IBD 发生得更快 过去 20 年来自拉丁美洲的移民。我们的收集工作非常成功 因为我们的地理位置以及我们对西班牙裔社区的承诺和参与。我们有独特的 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，也是最多元化的国家 原产地。我们准备在 IBDGC 拨款的支持下将我们的收集工作扩展到更广泛的州 佛罗里达州。全基因组关联研究（GWAS）促进了以前未被识别的发现 IBD 的基因和通路，并为公正地探索患者基因组提供了机会 患有炎症性肠病。我们将通过以下方式探索大量美国出生和外国出生的西班牙裔 IBD 病例的遗传变异： 专注于移民和第一代之间的目标基因组、转录组和表观遗传差异 患有 IBD 的西班牙裔美国人。我们将阐明基因和环境如何相互作用以产生不同的表型 IBD 的表现。我们的团队对先前精细绘制地图的方法具有特殊的专业知识和兴趣 确定风险位点并了解当地遗传血统对基因型-血统相互作用的影响 表型特征，目的是识别具有功能意义的遗传变异。我们的 拟议的研究将扩大对 IBD 疾病表型和遗传基础的了解 西班牙裔队列希望制定预防措施和改进治疗方法。 我们将利用两个 PI 的互补优势来推动发现并实现 NIDDK IBD 遗传学联盟 (IBDGC) 将扩大美国西班牙裔 IBD 患者的收集范围。