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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.
Involved Institutions
Details
| Item type | Article | ||||
| Journal or Publication Title | Nature Communications | ||||
| Publisher: | Nature | ||||
|---|---|---|---|---|---|
| Place of Publication: | LONDON | ||||
| Volume: | 9 | ||||
| Number of Issue or Book Chapter: | 1946 | ||||
| Page Range: | pp. 1-13 | ||||
| Date | 16 May 2018 | ||||
| Institutions | Medicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie | ||||
| Identification Number |
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| Keywords | GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; FAT; TISSUE; RISK; ARCHITECTURE; METAANALYSIS; INSIGHTS; DISEASE; BIOLOGY; | ||||
| Dewey Decimal Classification | 500 Science > 570 Life sciences | ||||
| Status | Published | ||||
| Refereed | Yes, this version has been refereed | ||||
| Created at the University of Regensburg | Yes | ||||
| URN of the UB Regensburg | urn:nbn:de:bvb:355-epub-374281 | ||||
| Item ID | 37428 |
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