| Title: | A joint view on genetic variants for adiposity differentiates subtypes with distinct metabolic implications |
| Journal: | Nature Communications |
| Published: | 16 May 2018 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/29769528/ |
| DOI: | https://doi.org/10.1038/s41467-018-04124-9 |
| URL: | https://www.nature.com/articles/s41467-018-04124-9.pdf |
Publication 8530
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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 × 10−8, 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.</p>
7 Authors
- Thomas W Winkler
- Felix Günther
- Simon Höllerer
- Martina Zimmermann
- Ruth JF Loos
- Zoltán Kutalik
- Iris M Heid
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