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

TitreA joint view on genetic variants for adiposity differentiates subtypes with distinct metabolic implications.
Publication TypeJournal Article
Year of Publication2018
AuthorsWinkler, TW, Günther, F, Höllerer, S, Zimmermann, M, Loos, RJf, Kutalik, Z, Heid, IM
JournalNature communications
Date Published05/2018
Mots-clésAdipose Tissue/metabolism, Adiposity/genetics, Body Mass Index, Energy Metabolism/genetics, Genetic Variation, Genome-Wide Association Study/methods, Humans, Meta-Analysis as Topic, Obesity/classification, Obesity/genetics, Obesity/metabolism, polymorphism, Single Nucleotide, Waist-Hip Ratio

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, 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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Alternate JournalNat Commun
Citation Key / SERVAL ID8869
Peer reviewRefereed
PubMed ID29769528
PubMed Central IDPMC5956079
Grant ListR01 DK075787 / DK / NIDDK NIH HHS / United States
R01 DK107786 / DK / NIDDK NIH HHS / United States
R01 DK110113 / DK / NIDDK NIH HHS / United States
U01 HG007417 / HG / NHGRI NIH HHS / United States


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