A joint view on genetic variants for adiposity differentiates subtypes with distinct metabolic implications.
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State: Public
Version: Final published version
State: Public
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
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
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 10:44
Last modification date
21/11/2022 8:22