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New genetic loci link adipose and insulin biology to body fat distribution.
Nature 518, 187-196 (2015)
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Genome-wide Association; Mesenchymal Stem-cells; Human Height; Adipogenic Differentiation; Abdominal Adiposity; Susceptibility Loci; Sexual-dimorphism; Glycemic Traits; False Discovery; Common Snps
ISSN (print) / ISBN
0028-0836
e-ISSN
1476-4687
Zeitschrift
Nature
Quellenangaben
Band: 518,
Heft: 7538,
Seiten: 187-196
Verlag
Nature Publishing Group
Verlagsort
London
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Epidemiology II (EPI2)
Institute of Genetic Epidemiology (IGE)
Institute of Human Genetics (IHG)
Institute of Epidemiology (EPI)
Institute for Pancreatic Beta Cell Research (IPI)
Institute of Genetic Epidemiology (IGE)
Institute of Human Genetics (IHG)
Institute of Epidemiology (EPI)
Institute for Pancreatic Beta Cell Research (IPI)