Multiomics study of nonalcoholic fatty liver disease

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Multiomics study of nonalcoholic fatty liver disease. / DBDS Genomic Consortium.

In: Nature Genetics, Vol. 54, 2022, p. 1652–1663.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

DBDS Genomic Consortium 2022, 'Multiomics study of nonalcoholic fatty liver disease', Nature Genetics, vol. 54, pp. 1652–1663. https://doi.org/10.1038/s41588-022-01199-5

APA

DBDS Genomic Consortium (2022). Multiomics study of nonalcoholic fatty liver disease. Nature Genetics, 54, 1652–1663. https://doi.org/10.1038/s41588-022-01199-5

Vancouver

DBDS Genomic Consortium. Multiomics study of nonalcoholic fatty liver disease. Nature Genetics. 2022;54:1652–1663. https://doi.org/10.1038/s41588-022-01199-5

Author

DBDS Genomic Consortium. / Multiomics study of nonalcoholic fatty liver disease. In: Nature Genetics. 2022 ; Vol. 54. pp. 1652–1663.

Bibtex

@article{e2abeedae15b41bca26f07866ba11131,
title = "Multiomics study of nonalcoholic fatty liver disease",
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.",
author = "Gardar Sveinbjornsson and Ulfarsson, {Magnus O.} and Thorolfsdottir, {Rosa B.} and Jonsson, {Benedikt A.} and Eythor Einarsson and Gylfi Gunnlaugsson and Solvi Rognvaldsson and Arnar, {David O.} and Magnus Baldvinsson and Bjarnason, {Ragnar G.} and Thjodbjorg Eiriksdottir and Christian Erikstrup and Egil Ferkingstad and Halldorsson, {Gisli H.} and Hannes Helgason and Anna Helgadottir and Lotte Hindhede and Grimur Hjorleifsson and David Jones and Knowlton, {Kirk U.} and Lund, {Sigrun H.} and Pall Melsted and Kristjan Norland and Isleifur Olafsson and Sigurdur Olafsson and Oskarsson, {Gudjon R.} and Ostrowski, {Sisse Rye} and Pedersen, {Ole Birger} and Snaebjarnarson, {Au{\dh}unn S.} and Emil Sigurdsson and Valgerdur Steinthorsdottir and Michael Schwinn and Gudmundur Thorgeirsson and Gudmar Thorleifsson and Ingileif Jonsdottir and Henning Bundgaard and Lincoln Nadauld and Bjornsson, {Einar S.} and Rulifson, {Ingrid C.} and Thorunn Rafnar and Norddahl, {Gudmundur L.} and Unnur Thorsteinsdottir and Patrick Sulem and Gudbjartsson, {Daniel F.} and Hilma Holm and Kari Stefansson and {DBDS Genomic Consortium}",
note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
doi = "10.1038/s41588-022-01199-5",
language = "English",
volume = "54",
pages = "1652–1663",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Multiomics study of nonalcoholic fatty liver disease

AU - Sveinbjornsson, Gardar

AU - Ulfarsson, Magnus O.

AU - Thorolfsdottir, Rosa B.

AU - Jonsson, Benedikt A.

AU - Einarsson, Eythor

AU - Gunnlaugsson, Gylfi

AU - Rognvaldsson, Solvi

AU - Arnar, David O.

AU - Baldvinsson, Magnus

AU - Bjarnason, Ragnar G.

AU - Eiriksdottir, Thjodbjorg

AU - Erikstrup, Christian

AU - Ferkingstad, Egil

AU - Halldorsson, Gisli H.

AU - Helgason, Hannes

AU - Helgadottir, Anna

AU - Hindhede, Lotte

AU - Hjorleifsson, Grimur

AU - Jones, David

AU - Knowlton, Kirk U.

AU - Lund, Sigrun H.

AU - Melsted, Pall

AU - Norland, Kristjan

AU - Olafsson, Isleifur

AU - Olafsson, Sigurdur

AU - Oskarsson, Gudjon R.

AU - Ostrowski, Sisse Rye

AU - Pedersen, Ole Birger

AU - Snaebjarnarson, Auðunn S.

AU - Sigurdsson, Emil

AU - Steinthorsdottir, Valgerdur

AU - Schwinn, Michael

AU - Thorgeirsson, Gudmundur

AU - Thorleifsson, Gudmar

AU - Jonsdottir, Ingileif

AU - Bundgaard, Henning

AU - Nadauld, Lincoln

AU - Bjornsson, Einar S.

AU - Rulifson, Ingrid C.

AU - Rafnar, Thorunn

AU - Norddahl, Gudmundur L.

AU - Thorsteinsdottir, Unnur

AU - Sulem, Patrick

AU - Gudbjartsson, Daniel F.

AU - Holm, Hilma

AU - Stefansson, Kari

AU - DBDS Genomic Consortium

N1 - Publisher Copyright: © 2022, The Author(s).

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85140761464&partnerID=8YFLogxK

U2 - 10.1038/s41588-022-01199-5

DO - 10.1038/s41588-022-01199-5

M3 - Journal article

C2 - 36280732

AN - SCOPUS:85140761464

VL - 54

SP - 1652

EP - 1663

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

ER -

ID: 330399387