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 (WHRadjBMI) at P < 5 x 10(-8), into four classes based on the direction of their effects on 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 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.
Highlights
We would like to clarify that the odds ratios reported in Results and Discussion of this article refer to disease risk increase per unit increase in BMI, where (i) BMI is standardized to a standard normal distribution (1 unit equivalent to one standard deviation of BMI, ~4.5 kg/m2), and (ii) this increase in BMI refers to the specific adiposity subtype
This should have been specified where the odds ratios were presented in the Results and Discussion sections of this article
These authors jointly supervised this work: Zoltán Kutalik, Iris M Heid
Summary
We would like to clarify that the odds ratios reported in Results and Discussion of this article refer to disease risk increase per unit increase in BMI, where (i) BMI is standardized to a standard normal distribution (1 unit equivalent to one standard deviation of BMI, ~4.5 kg/m2), and (ii) this increase in BMI refers to the specific adiposity subtype (given by the respective genetic variants’ class). Addendum: A joint view on genetic variants for adiposity differentiates subtypes with distinct metabolic implications Thomas W Winkler 1, Felix Günther1,2, Simon Höllerer1, Martina Zimmermann 1, Ruth JF Loos 3,4,5, Zoltán Kutalik6,7 & Iris M Heid1
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