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

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Version: Final published version
Serval ID
serval:BIB_20248F212AD0
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A joint view on genetic variants for adiposity differentiates subtypes with distinct metabolic implications.
Journal
Nature communications
Author(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
Publication state
Published
Issued date
16/05/2018
Peer-reviewed
Oui
Volume
9
Number
1
Pages
1946
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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.
Keywords
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
Yes
Create date
22/05/2018 11:44
Last modification date
20/08/2019 13:56
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