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Multi-SNP Analysis of GWAS Data Identifies Pathways Associated with Nonalcoholic Fatty Liver Disease

By Qing-rong Chen, Rosemary Braun, Ying Hu, Chunhua Yan, Elizabeth M. Brunt, Daoud Meerzaman, Arun J. Sanyal and Kenneth Buetow

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease; the histological spectrum of which ranges from steatosis to steatohepatitis. Nonalcoholic steatohepatitis (NASH) often leads to cirrhosis and development of hepatocellular carcinoma. To better understand pathogenesis of NAFLD, we performed the pathway of distinction analysis (PoDA) on a genome-wide association study dataset of 250 non-Hispanic white female adult patients with NAFLD, who were enrolled in the NASH Clinical Research Network (CRN) Database Study, to investigate whether biologic process variation measured through genomic variation of genes within these pathways was related to the development of steatohepatitis or cirrhosis. Pathways such as Recycling of eIF2:GDP, biosynthesis of steroids, Terpenoid biosynthesis and Cholesterol biosynthesis were found to be significantly associated with NASH. SNP variants in Terpenoid synthesis, Cholesterol biosynthesis and biosynthesis of steroids were associated with lobular inflammation and cytologic ballooning while those in Terpenoid synthesis were also associated with fibrosis and cirrhosis. These were also related to the NAFLD activity score (NAS) which is derived from the histological severity of steatosis, inflammation and ballooning degeneration. Eukaryotic protein translatio

Year: 2016
OAI identifier: oai:CiteSeerX.psu:10.1.1.789.4449
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