Research Project
10476656
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.
