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, Zoltan und Heid, Iris M. (2018): A joint view on genetic variants for adiposity differentiates subtypes with distinct metabolic implications. In: Nature Communications, Bd. 9, 1946

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Mathematik, Informatik und Statistik > Statistik
• Themengebiete: 500 Naturwissenschaften und Mathematik > 510 Mathematik
• ISSN: 2041-1723
• Sprache: Englisch