Titre
The link between liver fat and cardiometabolic diseases is highlighted by genome-wide association study of MRI-derived measures of body composition.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
van der Meer, D.
Auteure/Auteur
Gurholt, T.P.
Auteure/Auteur
Sønderby, I.E.
Auteure/Auteur
Shadrin, A.A.
Auteure/Auteur
Hindley, G.
Auteure/Auteur
Rahman, Z.
Auteure/Auteur
de Lange, A.G.
Auteure/Auteur
Frei, O.
Auteure/Auteur
Leinhard, O.D.
Auteure/Auteur
Linge, J.
Auteure/Auteur
Simon, R.
Auteure/Auteur
Beck, D.
Auteure/Auteur
Westlye, L.T.
Auteure/Auteur
Halvorsen, S.
Auteure/Auteur
Dale, A.M.
Auteure/Auteur
Karlsen, T.H.
Auteure/Auteur
Kaufmann, T.
Auteure/Auteur
Andreassen, O.A.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
2399-3642
Statut éditorial
Publié
Date de publication
2022-11-19
Volume
5
Numéro
1
Première page
1271
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Résumé
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.
PID Serval
serval:BIB_0F4A908C387A
PMID
Open Access
Oui
Date de création
2022-11-28T14:47:03.460Z
Date de création dans IRIS
2025-05-20T18:06:43Z
Fichier(s)![Vignette d'image]()
En cours de chargement...
Nom
36402844_BIB_0F4A908C387A.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
1.69 MB
Format
Adobe PDF
PID Serval
serval:BIB_0F4A908C387A.P001
URN
urn:nbn:ch:serval-BIB_0F4A908C387A7
Somme de contrôle
(MD5):76a776561ccc650ace2bedf791a36b52