Mount Sinai Regional Drug Induced Liver Injury Network Site

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。在她的航母上，尼克莱蒂博士 广泛研究药物性肝损伤的易感性，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，该项目对DILI病例进行了分析 基于HLA等位基因和常见变体她将继续发挥积极作用， 正在进行的GWAS和精细映射下游分析以及基于预测DILI风险 计算多基因风险评分。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 导致了几个DILIN出版物，但仍有更多的工作要做。去年，博士。 Nicoletti专注于识别和处理公开可用的数据集， 与DILIN病例大组的种族相匹配的人群对照。具有增强 Nicoletti博士说，由于大量新招募的DILIN样本的基因分型， 将导致发现与DILI作为表型或与药物治疗相关的新风险因素。 特异性DILI和先前鉴定的相关信号的复制。一项特别的努力将 研究合成代谢类固醇（AS）-DILI的遗传易感性。最后，自从博士。 Nicoletti发现了DILI可能与其他自身免疫性疾病共享遗传风险因素的证据， 对于原发性胆汁性肝硬化等肝脏疾病，Nicoletti博士将评估 DILI和其他肝脏疾病，以更好地了解DILI的病理生理学和DILI的作用。 自身免疫特性的遗传变异

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.