| Title: | Multiomics study of nonalcoholic fatty liver disease |
| Journal: | Nature Genetics |
| Published: | 24 Oct 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36280732/ |
| DOI: | https://doi.org/10.1038/s41588-022-01199-5 |
| URL: | https://www.nature.com/articles/s41588-022-01199-5.pdf |
Publication 10618
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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.</p>
46 Authors
- Gardar Sveinbjornsson
- Magnus O. Ulfarsson
- Rosa B. Thorolfsdottir
- Benedikt A. Jonsson
- Eythor Einarsson
- Gylfi Gunnlaugsson
- Solvi Rognvaldsson
- David O. Arnar
- Magnus Baldvinsson
- Ragnar G. Bjarnason
- Thjodbjorg Eiriksdottir
- Christian Erikstrup
- Egil Ferkingstad
- Gisli H. Halldorsson
- Hannes Helgason
- Anna Helgadottir
- Lotte Hindhede
- Grimur Hjorleifsson
- David Jones
- Kirk U. Knowlton
- Sigrun H. Lund
- Pall Melsted
- Kristjan Norland
- Isleifur Olafsson
- Sigurdur Olafsson
- Gudjon R. Oskarsson
- Sisse Rye Ostrowski
- Ole Birger Pedersen
- Auðunn S. Snaebjarnarson
- Emil Sigurdsson
- Valgerdur Steinthorsdottir
- Michael Schwinn
- Gudmundur Thorgeirsson
- Gudmar Thorleifsson
- Ingileif Jonsdottir
- Henning Bundgaard
- Lincoln Nadauld
- Einar S. Bjornsson
- Ingrid C. Rulifson
- Thorunn Rafnar
- Gudmundur L. Norddahl
- Unnur Thorsteinsdottir
- Patrick Sulem
- Daniel F. Gudbjartsson
- Hilma Holm
- Kari Stefansson
1 Application
| Application ID | Title |
|---|---|
| 56270 | Evaluating and comparing sequence variant associations between the deCODE and UK Biobank datasets across a range of human traits |
Enabling scientific discoveries that improve human health