A joint view on genetic variants for adiposity differentiates subtypes with distinct metabolic implications.

Détails

Ressource 1Télécharger: BIB_20248F212AD0.pdf (1866.46 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_20248F212AD0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A joint view on genetic variants for adiposity differentiates subtypes with distinct metabolic implications.
Périodique
Nature communications
Auteur⸱e⸱s
Winkler T.W., Günther F., Höllerer S., Zimmermann M., Loos R.J., Kutalik Z., Heid I.M.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
16/05/2018
Peer-reviewed
Oui
Volume
9
Numéro
1
Pages
1946
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
The problem of the genetics of related phenotypes is often addressed by analyzing adjusted-model traits, but such traits warrant cautious interpretation. Here, we adopt a joint view of adiposity traits in ~322,154 subjects (GIANT consortium). We classify 159 signals associated with body mass index (BMI), waist-to-hip ratio (WHR), or WHR adjusted for BMI (WHRadjBMI) at P < 5 × 10 <sup>-8</sup> , into four classes based on the direction of their effects on BMI and WHR. Our classes help differentiate adiposity genetics with respect to anthropometry, fat depots, and metabolic health. Class-specific Mendelian randomization reveals that variants associated with both WHR-decrease and BMI increase are linked to metabolically rather favorable adiposity through beneficial hip fat. Class-specific enrichment analyses implicate digestive systems as a pathway in adiposity genetics. Our results demonstrate that WHRadjBMI variants capture relevant effects of "unexpected fat distribution given the BMI" and that a joint view of the genetics underlying related phenotypes can inform on important biology.
Mots-clé
Adipose Tissue/metabolism, Adiposity/genetics, Body Mass Index, Energy Metabolism/genetics, Genetic Variation, Genome-Wide Association Study/methods, Humans, Meta-Analysis as Topic, Obesity/classification, Obesity/genetics, Obesity/metabolism, Polymorphism, Single Nucleotide, Waist-Hip Ratio
Pubmed
Web of science
Open Access
Oui
Création de la notice
22/05/2018 11:44
Dernière modification de la notice
21/11/2022 9:22
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