Winkler, Thomas W. and Guenther, Felix and Hoellerer, Simon and Zimmermann, Martina and Loos, Ruth J. F. and Kutalik, Zoltan and Heid, Iris M. (2018) A joint view on genetic variants for adiposity differentiates subtypes with distinct metabolic implications. NATURE COMMUNICATIONS, 9: 1946. ISSN 2041-1723,
Full text not available from this repository. (Request a copy)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), 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENOME-WIDE ASSOCIATION; BODY-MASS INDEX; FAT; TISSUE; RISK; ARCHITECTURE; METAANALYSIS; INSIGHTS; DISEASE; BIOLOGY; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Medicine > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Mar 2020 08:31 |
| Last Modified: | 23 Mar 2020 08:31 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14575 |
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