72 Establishing a histologically defined NAFLD cohort in the Million Veteran Program for further genetic analyses

Abstract

OBJECTIVES/GOALS: Research in Non Alcoholic Fatty Liver Disease Genetics is ongoing. In this project, we aim to: 1.Identify and describe a histological NAFLD Cohort in the MVP Biobank by extracting liver biopsy proven NAFLD patients using natural language processing (NLP) 2.Confirm previously defined NALFD genetic loci (via look up-GWAS) in the histological NLP cohort METHODS/STUDY POPULATION: We will utilize the Million Veteran Program Biobank where a total of 10,959 subjects have been identified using liver biopsy reports in the EMR via CPT codes. Cases will be based on i) steatosis, steatohepatitis, inflammation or fibrosis in liver biopsy reports with ii) exclusion of other causes of liver disease. Controls will be comprised of the general VA population. In collaboration with the Applied NLP and Precision Medicine groups at the VA Informatics and Computing Infrastructure(VINCI); we will attempt to create and validate a histological cohort of NAFLD in the MVP database by: 1)Annotation of biopsy reports for the NLP algorithm 2)Automation/training of the NLP algorithm We will then perform a multi-ancestry genetic lookup of previously established genetic loci among the cases identified. RESULTS/ANTICIPATED RESULTS: Recently published data: the MVP NAFLD research led by Dr. Chang and Dr. Vujkovic had first validated a proxy NAFLD phenotype based on chronic alanine aminotransferase elevation (cALT). A GWAS was then performed using this phenotype which revealed 77 loci of genome-wide significance including 10 established NAFLD- and 52 ALT-associated SNPs were identified. Replication in external Liver Biopsy and Imaging Cohorts validated 17 SNPs of which 9 were novel. Preliminary data on Liver Biopsy reports: Using CPT codes for Liver Biopsy we estimated a total of 10,959 unique patients and 18,812 notes in the MVP biobank. We anticipate 2,000-3,000 NAFLD cases (based on the prevalence of NAFLD in the general population). Initial review reveals 90% concordance between analysts for the purposes of developing an NLP. DISCUSSION/SIGNIFICANCE: NAFLD is a major cause for morbidity and mortality in liver disease. Gold standard for diagnosis is based on biopsy. GWAS studies with biopsy proven phenotypes are limited. The study will aim to isolate a histologically defined NAFLD cohort in MVP to conduct further GWAS that can provide new clinically relevant knowledge for future research.

Contemporary Research Challenges