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: 10476656
• 负责人: Jawad Ahmad
• 金额: $ 14.62万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10476656
• 关键词: Adverse event; Alleles; Anabolic steroids; Autoimmune; Biological Markers; Collaborations; Data Set; Diagnosis; Ethnic Origin; Functional disorder; Genetic; Genetic Markers; Genetic Predisposition to Disease; Genetic study; Genotype; Goals; Herbal supplement; Lead; Liver diseases; Nature; Patients; Pharmaceutical Preparations; Phenotype; Population Control; Predisposition; Primary biliary cirrhosis; Prognosis; Publications; Research Personnel; Risk; Risk Factors; Role; Sampling; Signal Transduction; Site; Variant; Work; base; case-based; design; experience; genetic analysis; genetic risk factor; genetic variant; genome wide association study; genome-wide; liver injury; novel; patient stratification; personalized predictions; polygenic risk score; precision medicine; prediction algorithm; predictive marker; recruit; 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. In course of her carrier, Dr. Nicoletti has been working extensively on the predisposition to drug induced liver injury and 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 fine-mapping downstream analyses and on predicting DILI risk based on calculation of Polygenic Risk Score. Given her extensive experience on HLA allele prediction algorithms and subsequent association analyses, Dr. Nicoletti will continue leading studies within DILIN HLA allele sequencing project in collaboration with other DILIN researchers. These efforts led to several DILIN publications, but additional work remains to be done. In the past year, Dr. Nicoletti focused her efforts in identifying and processing publicly available datasets to select population controls that match the ethnicities of the large group of DILIN cases. With an enhanced statistical power due to the genotyping of a large set of newly recruited DILIN samples, Dr Nicoletti will lead the discovery of novel risk factors associated with DILI as phenotype or with Drug specific-DILI and the replication of previously identified association signals. A particular effort will be devolved to study the genetic susceptibility of Anabolic Steroid (AS)-DILI. Finally, since Dr. Nicoletti discovered evidence that DILI might share genetic risk factors with other autoimmune liver diseases like primary biliary cirrhosis, Dr Nicoletti will evaluate the genetic similarity between DILI and other liver disease to better understand the pathophysiology of DILI and the role of the genetic variants in the autoimmune traits.

项目概要 自成立以来 DILIN 的一个主要目标就是识别可预测的遗传生物标志物 DILI 易感性和预后不良。 DILIN 已识别出特定药物和一般药物 DILI 易感性的生物标志物。在她的携带过程中，尼科莱蒂博士一直在工作 广泛研究药物引起的肝损伤倾向并加入 DILIN 联盟。博士。 Nicoletti 一直积极参与正在进行的 DILIN 基因项目，该项目描述了 DILI 病例 基于 HLA 等位基因和常见变异。她将继续发挥积极作用 进行正在进行的 GWAS 和精细映射下游分析，并基于预测 DILI 风险 关于多基因风险评分的计算。鉴于她在 HLA 等位基因预测方面的丰富经验 算法和随后的关联分析，Nicoletti 博士将继续在 DILIN HLA 等位基因测序项目与其他 DILIN 研究人员合作。这些努力 导致了几篇 DILIN 出版物，但仍有更多工作要做。在过去的一年里，博士。 Nicoletti 致力于识别和处理公开可用的数据集以选择 与大量 DILIN 病例的种族相匹配的人口控制。具有增强的 Nicoletti 博士对大量新招募的 DILIN 样本进行了基因分型，具有统计功效 将导致与 DILI 表型或药物相关的新危险因素的发现 特异性 DILI 和先前识别的关联信号的复制。特别的努力将 致力于研究合成代谢类固醇（AS）-DILI 的遗传易感性。最后，自从博士。 Nicoletti 发现证据表明 DILI 可能与其他自身免疫性疾病有共同的遗传风险因素 对于原发性胆汁性肝硬化等肝脏疾病，Nicoletti 博士将评估两者之间的遗传相似性 DILI 和其他肝脏疾病，以更好地了解 DILI 的病理生理学及其作用 自身免疫特征的遗传变异。