The link between liver fat and cardiometabolic diseases is highlighted by genome-wide association study of MRI-derived measures of body composition.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_0F4A908C387A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The link between liver fat and cardiometabolic diseases is highlighted by genome-wide association study of MRI-derived measures of body composition.
Journal
Communications biology
Author(s)
van der Meer D., Gurholt T.P., Sønderby I.E., Shadrin A.A., Hindley G., Rahman Z., de Lange A.G., Frei O., Leinhard O.D., Linge J., Simon R., Beck D., Westlye L.T., Halvorsen S., Dale A.M., Karlsen T.H., Kaufmann T., Andreassen O.A.
ISSN
2399-3642 (Electronic)
ISSN-L
2399-3642
Publication state
Published
Issued date
19/11/2022
Peer-reviewed
Oui
Volume
5
Number
1
Pages
1271
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
Obesity and associated morbidities, metabolic associated fatty liver disease (MAFLD) included, constitute some of the largest public health threats worldwide. Body composition and related risk factors are known to be heritable and identification of their genetic determinants may aid in the development of better prevention and treatment strategies. Recently, large-scale whole-body MRI data has become available, providing more specific measures of body composition than anthropometrics such as body mass index. Here, we aimed to elucidate the genetic architecture of body composition, by conducting genome-wide association studies (GWAS) of these MRI-derived measures. We ran both univariate and multivariate GWAS on fourteen MRI-derived measurements of adipose and muscle tissue distribution, derived from scans from 33,588 White European UK Biobank participants (mean age of 64.5 years, 51.4% female). Through multivariate analysis, we discovered 100 loci with distributed effects across the body composition measures and 241 significant genes primarily involved in immune system functioning. Liver fat stood out, with a highly discoverable and oligogenic architecture and the strongest genetic associations. Comparison with 21 common cardiometabolic traits revealed both shared and specific genetic influences, with higher mean heritability for the MRI measures (h <sup>2 </sup> = .25 vs. .13, p = 1.8x10 <sup>-7</sup> ). We found substantial genetic correlations between the body composition measures and a range of cardiometabolic diseases, with the strongest correlation between liver fat and type 2 diabetes (r <sub>g </sub> = .49, p = 2.7x10 <sup>-22</sup> ). These findings show that MRI-derived body composition measures complement conventional body anthropometrics and other biomarkers of cardiometabolic health, highlighting the central role of liver fat, and improving our knowledge of the genetic architecture of body composition and related diseases.
Keywords
Humans, Female, Middle Aged, Male, Genome-Wide Association Study, Diabetes Mellitus, Type 2, Body Composition/genetics, Liver/diagnostic imaging, Magnetic Resonance Imaging, Cardiovascular Diseases
Pubmed
Web of science
Open Access
Yes
Create date
28/11/2022 15:47
Last modification date
23/01/2024 7:20
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