Determining genetic and microbiome effects on non-alcoholic fatty liver disease and its medical complications in a Chinese population

JI Program: Liver/GI

Nonalcoholic fatty liver disease has increased with the rise of obesity and can contribute to liver and cardiometabolic disease. We identified genetic subtypes of NAFLD and environmental causes of NAFLD in genetically predisposed individuals. This work was mostly performed in individuals of European ancestry. Individuals of Asian ancestry have higher rates of metabolic disease including NAFLD controlling for obesity than individuals of European ancestry. Whether this is genetically or environmentally mediated is not known. Further, microbiota have been shown to influence obesity and NAFLD in small populations but their effect in large populations is not known. Here we collected a large well characterized population based cohort from Pinggu China where there is an explosion of metabolic disease. We have excellent measures of NAFLD, DNA, stool and a wealth of covariates. We now aim to genotype the cohort, carry out metagenomic analyses from stool, and collect follow up data on incident liver and cardiometabolic disease. We will then carry out analyses to define genetic and microbiome influences on prevalent NAFLD as well as the effect of NAFLD and its precipitants on incident liver and cardiometabolic disease. Results from this work will define genetic and environmental causes of NAFLD to help further refine treatments and precision care of patients with NAFLD.