PROJECT SUMMARY/ABSTRACT - SUPPLEMENT NIAAA recognized the critical need to develop rationally-based therapies for alcoholic hepatitis (AH) and established the Alcoholic Hepatitis Consortia (ASH U01) in 2012/2013, funding four independent consortia to conduct clinical and translational studies in patients with moderate to severe alcoholic hepatitis. While each of the four consortia developed independent clinical approaches, the collection of genetic material, as well as an extensive phenotypic analysis of all patients, was a common theme amongst the four groups. In this U01, which is an extramural/intramural collaboration with Dr. David Goldman in the Laboratory of Neurogenetics (LNG) at NIAAA, we are combining the efforts of all four consortia, and the ongoing support from Dr. Bruce Barton with the AlcHepNet Data Coordinating Center at UMASS, in order to leverage these important biospecimens and clinical data into a single cohort large enough for investigations into the genetic contributions to AH. In addition, whole exome sequence data, collected by the NIH/NIAAA Clinical Center, will be available from ~800 heavy drinkers without liver disease to serve as an important control cohort. Specific Aim 1: COMPLETED Whole exome sequencing (WES) of the DNA from patients with AH, as well as a cohort of heavy drinking controls without liver disease: This aim is completed. WES was carried out in years 1-3 by LNG and then data were transferred to Indiana University and processed through their data cleaning pipeline Specific Aim 2: DELAYED START: Novel analytical approaches to determine genetic risk for key determinants of AH: Our original plan was to begin analysis in Year 4. However, we lost time due to the COVID-19 pandemic. We incurred delays determining where and how to transfer and store the data, with the eventual decision to store it at UMASS/MGHPCC. Getting access to the UMASS/MGHPCC server was considerably delayed, related to most of the administrators working from home during the pandemic. Similar administrative delays in year 4 occurred as we finalized all the MTAs/DUAs between institutions; all the necessary permissions and access procedures just took much longer than usual during the pandemic-limited work environment. Administrative Supplement Request: Because of these delays related to the pandemic, we would like to request an Administrative Supplement to handle the increased cost for data analysis in year 5 of our grant. By adding effort for PIs and their staff, we will be able to speed up the genomic analysis of the data and make up for lost time during the pandemic. The plan for year 5 is to determine genetics for susceptibility and severity of AH and publish a manuscript on the results. The goals of the proposed supplement are well within the original Council-approved scope of the research and does not move in new directions; the supplement will be used solely to make up for lost time in the analysis of the data during year 4 of the grant...