Mount Sinai Regional Drug Induced Liver Injury Network Site

西奈山地区药物性肝损伤网络网站

• 批准号: 10198195
• 负责人: Jawad Ahmad
• 金额: $ 6.59万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-15 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10198195
• 关键词: Alleles; Autoimmune Process; Biological Markers; Clinic; Clinical Data; Collaborations; Data; Data Set; Diagnosis; Drug Exposure; Enrollment; Fruit; Functional disorder; Genetic; Genetic Markers; Genotype; Goals; Haplotypes; Herbal supplement; Home environment; Individual; Link; Liver; Liver diseases; Medical center; Nature; Patient Recruitments; Patients; Pharmaceutical Preparations; Positioning Attribute; Predisposition; Primary biliary cirrhosis; Publications; Research Personnel; Role; Site; Time; Variant; Work; base; biobank; case-based; database of Genotypes and Phenotypes; design; disorder control; experience; genetic risk factor; genetic variant; genome wide association study; high risk; improved; liver injury; non-drug; outcome forecast; prediction algorithm; predictive marker; trait

Project Summary A major goal of DILIN since its inception has been to identify genetic biomarkers that predict predisposition to DILI and a poor prognosis. DILIN has identified both drug specific and general biomarkers for predisposition to DILI. The majority of these genetic biomarkers involve HLA alleles. In the last several years, Dr. Nicoletti has been working extensively on the predisposition to drug induced liver injury and recently joined the DILIN consortium. Dr. Nicoletti has been actively involved in the ongoing DILIN genetic projects that profiled DILI cases based on HLA alleles and common variants. She will continue to take an active role in carrying out the ongoing GWAS and PrediXscan analyses. Given her extensive experience on HLA allele prediction algorithms using both genotyped and sequencing data and extensive experience on the subsequent association analyses at the level of HLA alleles, haplotypes, and HLA supertypes, Dr. Nicoletti is also directing the design/analysis and interpretation of the results of the DILIN HLA allele sequencing project in collaboration with Dr. Li, Dr. Chalasani, Dr. Barnhart, Dr. Phillips and other DILIN researchers. Appropriate non-DILI control data will be critical to these studies. These efforts led to several DILIN publications in the past year, but additional work remains to be done. In the past year, Dr. Nicoletti expanded her efforts dramatically to provide non-DILI control data and investigate genetic links between predisposition to DILI and other liver diseases. Dr. Nicoletti is in the unique position of having immediate access to drug exposed and disease controls via the Mount Sinai BioME Biobank, one of the largest biobanks, which has paired genetic and clinical data for more than 50,000 individuals. This biobank is heavily weighted towards those with liver disease since the liver division was the first to open its clinic patients to enrollment in BioME. Finally, Dr. Nicoletti discovered evidence that DILI might share genetic risk factors with other autoimmune liver diseases like primary biliary cirrhosis. By combining DILIN genetic data with the BioMe dataset and other appropriate dbGAP datasets, she hopes to evaluate the genetic similarity between DILI and other liver disease in order to better understand the pathophysiology of DILI and the role of the genetic variants in the autoimmune traits. Additional time and effort is needed to bring these studies to fruition. DILIN is requesting another year of supplemental support for Dr. Nicoletti's efforts.

项目摘要 DILIN自成立以来的一个主要目标是鉴定预测以下疾病的遗传生物标志物： 易患DILI和预后不良。DILIN已确定药物特异性和一般性 DILI易感性的生物标志物。这些遗传生物标志物中的大多数涉及HLA 等位基因。 在过去的几年里，Nicoletti博士一直在广泛研究 药物引起的肝损伤，最近加入了DILIN联盟。尼克莱蒂医生 积极参与正在进行的DILIN基因项目，该项目基于HLA对DILI病例进行了分析 等位基因和常见变体。她将继续发挥积极作用， GWAS和PrediXscan分析。鉴于她在HLA等位基因预测方面的丰富经验 使用基因分型和测序数据的算法以及 随后在HLA等位基因、单倍型和HLA超型水平上进行关联分析， 博士Nicoletti还指导DILIN结果的设计/分析和解释 与李博士、查拉萨尼博士、巴恩哈特博士、李博士合作的HLA等位基因测序项目。 菲利普斯和其他DILIN研究人员。适当的非DILI对照数据将是关键， 问题研究通过这些努力，在过去一年里出版了几本DILIN出版物，但还开展了更多的工作， 仍有待完成。 在过去的一年里，Nicoletti博士大大扩大了她的努力，提供非DILI对照数据 并研究DILI易感性与其他肝脏疾病之间的遗传联系。博士 Nicoletti处于独特的地位，可以立即接触到暴露的药物和疾病， 通过西奈山生物医学生物银行进行控制，这是最大的生物银行之一， 超过50，000人的遗传和临床数据。这个生物库的权重很大 自肝脏部门第一次开放诊所患者以来， 加入BioME最后，Nicoletti博士发现了DILI可能具有遗传风险的证据。 其他自身免疫性肝病如原发性胆汁性肝硬化的因素。通过结合DILIN 基因数据与BioMe数据集和其他适当的dbGAP数据集，她希望 评估DILI与其他肝病之间的遗传相似性，以便更好地了解 DILI的病理生理学和遗传变异在自身免疫性状中的作用。 需要更多的时间和努力才能使这些研究取得成果。迪林要求 为尼科莱蒂医生的努力再提供一年的支持