IBD Gene Mapping by Clinical and Population Subset

项目总结 炎症性肠病(IBD)、克罗恩病(CD)和溃疡性结肠炎(UC)是复杂的遗传因素 胃肠道疾病，是患者和社会的主要健康负担。多中心 来自6个遗传学研究中心(GRC)的协作研究，由数据协调中心组织 (DCC)成立NIDDK IBD遗传学联盟(IBDGC)在以下方面做出了巨大贡献 用全基因组关联研究鉴定200多个IBD基因座剖析IBD遗传病因学 (GWAS)。我们的GRC为IBDGC的所有研究做出了贡献，并担任过IBDGC的领导职位。 我们特别的GRC重点是揭示和表征IBD的遗传病因，以及 非洲裔美国人群体中的表型表达和病程。我们将继续招聘 并仔细对患有IBD的非裔美国人患者进行表型，以最大限度地发挥遗传和表型的力量 调查。我们还将招募患者参加以西班牙裔/拉丁裔为重点的IBDGC平行研究 人口。我们将通过以下方式扩大和细化导致非裔美国人IBD遗传风险的IBD基因座 进一步采用性别分层和精细作图的方法，并评估基因-表型 联想。我们将进行多重免疫疾病关联荟萃分析聚合基因组- 广泛的数据以最大限度地提高识别常见免疫介导性疾病基因座的能力，同时还表征 在所评估的性状中具有多效性。我们将为从西方分离的免疫细胞提供关键资源- 并生成基因表达和表观遗传学数据以实现共定位 更好地定义致病变异及其对导致遗传风险的基因表达的影响 非裔美国人中的IBD。最后，我们将继续参加所有IBDGC活动，以 通过这种合作资助机制，最大限度地发挥IBD遗传学研究的影响。

PROJECT SUMMARY Inflammatory bowel disease (IBD), Crohn’s disease (CD) and ulcerative colitis (UC) are complex genetic disorders of the gastrointestinal tract, and a major health burden to patients and society. Multicenter collaborative studies from 6 Genetics Research Centers (GRCs), organized with a Data Coordinating Center (DCC) to form the NIDDK IBD Genetics Consortium (IBDGC) has contributed to tremendous progress in dissecting IBD genetic etiology with identification of over 200 IBD loci by genome wide association studies (GWAS). Our GRC has contributed to all IBDGC studies and has taken roles in IBDGC leadership positions. Our particular GRC focus is uncovering and characterizing the genetic etiology of IBD, and variations in phenotypic expressivity and disease course, in the African-American population. We will continue to recruit and carefully phenotype African-American patients with IBD to maximize power for genetic and phenotype investigations. We will also recruit patients for parallel IBDGC focused studies in the Hispanic/LatinX population. We will expand and refine IBD loci contributing to the genetic risk of IBD in African-Americans by further GWAS, with sex-stratified, and fine-mapping approaches, and evaluate genotype-phenotype associations. We will perform a multiple immune disease association meta-analyses aggregating genome- wide data to maximize power to identify common immune mediated disease loci while also characterizing pleiotropy among the traits evaluated. We will provide critical resources in immune cells isolated from West- Africans and African-Americans and generate gene expression and epigenetic data for colocalization to better define disease causing variants and their effect on gene expression that result in the genetic risks of IBD in the African-American population. Lastly we will continue to participate in all IBDGC activities to maximize the impact of IBD genetics research by this cooperative funding mechanism.