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Winkler, Thomas W. ; Günther, Felix ; Höllerer, Simon ; Zimmermann, Martina ; Loos, Ruth J. F. ; Kutalik, Zoltán ; Heid, Iris M.

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

Winkler, Thomas W. , Günther, Felix, Höllerer, Simon, Zimmermann, Martina , Loos, Ruth J. F. , Kutalik, Zoltán and Heid, Iris M. (2018) A joint view on genetic variants for adiposity differentiates subtypes with distinct metabolic implications. Nature Communications 9 (1946), pp. 1-13.

Date of publication of this fulltext: 22 Apr 2021 13:59
Article
DOI to cite this document: 10.5283/epub.37428


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 similar to 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 x 10(-8), ...

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 similar to 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 x 10(-8), 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.



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Details

Item typeArticle
Journal or Publication TitleNature Communications
Publisher:Nature
Place of Publication:LONDON
Volume:9
Number of Issue or Book Chapter:1946
Page Range:pp. 1-13
Date16 May 2018
InstitutionsMedicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie
Identification Number
ValueType
10.1038/s41467-018-04124-9DOI
KeywordsGENOME-WIDE ASSOCIATION; BODY-MASS INDEX; FAT; TISSUE; RISK; ARCHITECTURE; METAANALYSIS; INSIGHTS; DISEASE; BIOLOGY;
Dewey Decimal Classification500 Science > 570 Life sciences
StatusPublished
RefereedYes, this version has been refereed
Created at the University of RegensburgYes
URN of the UB Regensburgurn:nbn:de:bvb:355-epub-374281
Item ID37428

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