IBD Gene Mapping by Clinical and Population Subset

按临床和人群亚群划分的 IBD 基因图谱

• 批准号: 10707288
• 负责人: Steven R Brant
• 金额: $ 49.83万
• 依托单位: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
• 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/10707288
• 关键词: ATAC-seq; Admixture; African; African American; African American population; African ancestry; Alleles; American; Caring; Cell Separation; Cells; Centers for Disease Control and Prevention (U.S.); Chromatin; Chromosome Mapping; Chronic; Clinical; Complex; Crohn' s disease; Data; Data Coordinating Center; Diagnosis; Digestive System Disorders; Disease; East Asian; Epigenetic Process; European; Evaluation; Financial Hardship; Funding Mechanisms; Gastrointestinal Diseases; Gene Expression; Gene Targeting; Genes; Genetic; Genetic Counseling; Genetic Diseases; Genetic Predisposition to Disease; Genetic Research; Genetic Risk; Genetic Variation; Genome; Genotype; Goals; Health; Hispanic; Immune; Immune System Diseases; Inflammatory Bowel Diseases; International; Investigation; Knowledge; Latinx population; Leadership; Linkage Disequilibrium; Literature; Maps; Mediating; Medical; Meta-Analysis; Molecular Genetics; National Institute of Diabetes and Digestive and Kidney Diseases; Outcome; Participant; Patient Recruitments; Patient-Focused Outcomes; Patients; Phenotype; Play; Population; Positioning Attribute; Postoperative Period; Prevalence; Prevention strategy; Preventive measure; Probability; Quality of Care; Recurrent disease; Research; Resources; Risk; Risk Factors; Role; Sensitivity and Specificity; Societies; Specialist; Structure; TNFSF15 gene; Ulcerative Colitis; Untranslated RNA; Variant; X Chromosome; diagnostic algorithm; disease phenotype; genetic association; genetic risk factor; genetic variant; genome sequencing; genome wide association study; genome-wide; improved; insight; multiple omics; new therapeutic target; novel; pleiotropism; rare variant; receptor; recruit; risk variant; sex; targeted treatment; trait; transcriptome; transcriptome sequencing; treatment disparity; treatment planning; whole genome

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.

项目概要 炎症性肠病（IBD）、克罗恩病（CD）和溃疡性结肠炎（UC）是复杂的遗传性疾病 胃肠道疾病，给患者和社会带来重大健康负担。多中心 来自 6 个遗传学研究中心 (GRC) 的合作研究，由数据协调中心组织 (DCC) 组建 NIDDK IBD 遗传学联盟 (IBDGC) 为在 通过全基因组关联研究鉴定 200 多个 IBD 位点，剖析 IBD 遗传病因 （GWAS）。我们的 GRC 为所有 IBDGC 研究做出了贡献，并担任了 IBDGC 的领导职务。 我们的 GRC 特别关注的是揭示和描述 IBD 的遗传病因以及 IBD 的变异 非裔美国人的表型表达和疾病过程。我们将继续招募 并仔细对非裔美国 IBD 患者进行表型分析，以最大限度地发挥遗传和表型的作用 调查。我们还将招募患者进行西班牙裔/拉丁裔平行 IBDGC 重点研究 人口。我们将通过以下方式扩展和完善导致非裔美国人 IBD 遗传风险的 IBD 基因座： 进一步的 GWAS，采用性别分层和精细作图方法，并评估基因型-表型 协会。我们将进行多种免疫疾病关联荟萃分析，汇总基因组- 广泛的数据，以最大限度地提高识别常见免疫介导疾病位点的能力，同时也表征 评估的性状之间的多效性。我们将提供从西方分离的免疫细胞的关键资源- 非洲人和非裔美国人并生成基因表达和表观遗传数据以进行共定位 更好地定义致病变异及其对基因表达的影响，从而导致遗传风险 非裔美国人中的 IBD。最后，我们将继续参与所有 IBDGC 活动 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。

项目成果

An increase in LRRK2 suppresses autophagy and enhances Dectin-1-induced immunity in a mouse model of colitis.

• DOI: 10.1126/scitranslmed.aan8162
• 发表时间: 2018-06-06
• 期刊: Science translational medicine
• 影响因子: 17.1
• 作者: Takagawa T;Kitani A;Fuss I;Levine B;Brant SR;Peter I;Tajima M;Nakamura S;Strober W
• 通讯作者: Strober W

Impact of Genotype, Serum Bile Acids, and Surgical Biliary Diversion on Native Liver Survival in FIC1 Deficiency.

• DOI: 10.1002/hep.31787
• 发表时间: 2021-08
• 期刊: Hepatology (Baltimore, Md.)
• 作者: van Wessel DBE;Thompson RJ;Gonzales E;Jankowska I;Shneider BL;Sokal E;Grammatikopoulos T;Kadaristiana A;Jacquemin E;Spraul A;Lipiński P;Czubkowski P;Rock N;Shagrani M;Broering D;Algoufi T;Mazhar N;Nicastro E;Kelly D;Nebbia G;Arnell H;Fischler B;Hulscher JBF;Serranti D;Arikan C;Debray D;Lacaille F;Goncalves C;Hierro L;Muñoz Bartolo G;Mozer-Glassberg Y;Azaz A;Brecelj J;Dezsőfi A;Luigi Calvo P;Krebs-Schmitt D;Hartleif S;van der Woerd WL;Wang JS;Li LT;Durmaz Ö;Kerkar N;Hørby Jørgensen M;Fischer R;Jimenez-Rivera C;Alam S;Cananzi M;Laverdure N;Targa Ferreira C;Ordonez F;Wang H;Sency V;Mo Kim K;Chen HL;Carvalho E;Fabre A;Quintero Bernabeu J;Alonso EM;Sokol RJ;Suchy FJ;Loomes KM;McKiernan PJ;Rosenthal P;Turmelle Y;Rao GS;Horslen S;Kamath BM;Rogalidou M;Karnsakul WW;Hansen B;Verkade HJ;Natural Course and Prognosis of PFIC and Effect of Biliary Diversion Consortium
• 通讯作者: Natural Course and Prognosis of PFIC and Effect of Biliary Diversion Consortium

Patient trust-in-physician and race are predictors of adherence to medical management in inflammatory bowel disease.

• DOI: 10.1002/ibd.20883
• 发表时间: 2009-08
• 期刊: INFLAMMATORY BOWEL DISEASES
• 影响因子: 4.9
• 作者: Nguyen, Geoffrey C.;LaVeist, Thomas A.;Harris, Mary L.;Datta, Lisa W.;Bayless, Theodore M.;Brant, Steven R.
• 通讯作者: Brant, Steven R.

Recent insights into the genetics of inflammatory bowel disease.

• DOI: 10.1053/j.gastro.2011.02.046
• 发表时间: 2011-05
• 期刊: Gastroenterology
• 影响因子: 29.4
• 作者: Cho JH;Brant SR
• 通讯作者: Brant SR

Inflammatory Bowel Diseases Before and After 1990.

• DOI: 10.1016/j.gastha.2022.08.001
• 发表时间: 2023
• 期刊: Gastro hep advances
• 作者: Truta, Brindusa;Begum, Ferdouse;Datta, Lisa Wu;Brant, Steven R
• 通讯作者: Brant, Steven R