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Multiomics study of nonalcoholic fatty liver disease

Multiomics study of nonalcoholic fatty liver disease


Title: Multiomics study of nonalcoholic fatty liver disease
Author: DBDS Genomic Consortium
Date: 2022-10-24
Language: English
Scope: 12
University/Institute: Landspitali - The National University Hospital of Iceland
School: Health Sciences
Department: Faculty of Electrical and Computer Engineering
Faculty of Medicine
Cardio-Vascular Center
Women's and Childrens's Services
Faculty of Industrial Engineering, Mechanical Engineering and Computer Science
Faculty of Physical Sciences
Clinical Laboratory Services, Diagnostics and Blood Bank
Internal Medicine and Emergency Services
Other departments
Office of Division of Clinical Services I
Series: Nature Genetics; 54(11)
ISSN: 1061-4036
DOI: https://doi.org/10.1038/s41588-022-01199-5
Subject: Lífefna- og sameindalíffræði; Meltingarlæknisfræði; Barnalæknisfræði; Hjartalæknisfræði; Náttúrufræðingar; Humans; Non-alcoholic Fatty Liver Disease/genetics; Proteomics; Genome-Wide Association Study; Liver/metabolism; Liver Cirrhosis/genetics; Liver Neoplasms/genetics; Genetics
URI: https://hdl.handle.net/20.500.11815/3598

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Citation:

DBDS Genomic Consortium 2022 , ' Multiomics study of nonalcoholic fatty liver disease ' , Nature Genetics , vol. 54 , no. 11 , pp. 1652-1663 . https://doi.org/10.1038/s41588-022-01199-5

Abstract:

Nonalcoholic fatty liver (NAFL) and its sequelae are growing health problems. We performed a genome-wide association study of NAFL, cirrhosis and hepatocellular carcinoma, and integrated the findings with expression and proteomic data. For NAFL, we utilized 9,491 clinical cases and proton density fat fraction extracted from 36,116 liver magnetic resonance images. We identified 18 sequence variants associated with NAFL and 4 with cirrhosis, and found rare, protective, predicted loss-of-function variants in MTARC1 and GPAM, underscoring them as potential drug targets. We leveraged messenger RNA expression, splicing and predicted coding effects to identify 16 putative causal genes, of which many are implicated in lipid metabolism. We analyzed levels of 4,907 plasma proteins in 35,559 Icelanders and 1,459 proteins in 47,151 UK Biobank participants, identifying multiple proteins involved in disease pathogenesis. We show that proteomics can discriminate between NAFL and cirrhosis. The present study provides insights into the development of noninvasive evaluation of NAFL and new therapeutic options.

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Publisher Copyright: © 2022, The Author(s).

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