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. © 2015 Macmillan Publishers Limited. All rights reserved.

New genetic loci link adipose and insulin biology to body fat distribution

VERONESI, GIOVANNI;
2015-01-01

Abstract

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. © 2015 Macmillan Publishers Limited. All rights reserved.
2015
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adiponectin; high density lipoprotein cholesterol; insulin; insulin receptor; low density lipoprotein cholesterol; peroxisome proliferator activated receptor; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; triacylglycerol; vasculotropin, developmental biology; fat; gene expression; genetic analysis; genome; genomics; numerical model, adipocyte; adipose tissue; amino acid sequence; angiogenesis; Article; body fat distribution; body mass; European; female; gene cluster; gene expression; gene locus; gene mapping; gene structure; genetic association; genetic correlation; genetic regulation; genetic variability; heritability; hip circumference; histone modification; human; insulin resistance; lipoprotein blood level; major clinical study; male; meta analysis (topic); molecular biology; obesity; priority journal; protein protein interaction; sex difference; single nucleotide polymorphism; subcutaneous fat; tissue level; transcription initiation site; transcription regulation; triacylglycerol blood level; waist circumference; waist hip ratio
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11383/2020384
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