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

Shungin, Dmitry LU ; Winkler, Thomas W; Croteau-Chonka, Damien C; Ferreira, Teresa; Locke, Adam E; Mägi, Reedik; Strawbridge, Rona J; Pers, Tune H; Fischer, Krista and Justice, Anne E, et al. (2015) In Nature 518(7538). p.187-378
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... (More)
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. (Less)
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Obesity: genetics, Physiologic: genetics, Neovascularization, Insulin Resistance: genetics, Insulin: metabolism, Human: genetics, Genome, Europe: ethnology, Continental Population Groups: genetics, Adipose Tissue: metabolism, Adipocytes: metabolism, Adipogenesis: genetics, Polymorphism, Single Nucleotide: genetics, Quantitative Trait Loci: genetics, Transcription, Genetic: genetics
in
Nature
volume
518
issue
7538
pages
187 - 378
publisher
Nature Publishing Group
external identifiers
  • pmid:25673412
  • wos:000349190300030
  • scopus:84923169934
ISSN
0028-0836
DOI
10.1038/nature14132
language
English
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yes
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3e5c03cd-7b22-4d63-b18b-b30b066e7fe9 (old id 5144408)
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http://www.ncbi.nlm.nih.gov/pubmed/25673412?dopt=Abstract
date added to LUP
2015-03-07 12:09:19
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2017-11-19 03:22:59
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  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 &lt; 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.},
  author       = {Shungin, Dmitry and Winkler, Thomas W and Croteau-Chonka, Damien C and Ferreira, Teresa and Locke, Adam E and Mägi, Reedik and Strawbridge, Rona J and Pers, Tune H and Fischer, Krista and Justice, Anne E and Workalemahu, Tsegaselassie and Wu, Joseph M W and Buchkovich, Martin L and Heard-Costa, Nancy L and Roman, Tamara S and Drong, Alexander W and Song, Ci and Gustafsson, Stefan and Day, Felix R and Esko, Tonu and Fall, Tove and Kutalik, Zoltán and Luan, Jian'an and Randall, Joshua C and Scherag, André and Vedantam, Sailaja and Wood, Andrew R and Chen, Jin and Fehrmann, Rudolf and Karjalainen, Juha and Kahali, Bratati and Liu, Ching-Ti and Schmidt, Ellen M and Absher, Devin and Amin, Najaf and Anderson, Denise and Beekman, Marian and Bragg-Gresham, Jennifer L and Buyske, Steven and Demirkan, Ayse and Ehret, Georg B and Feitosa, Mary F and Goel, Anuj and Jackson, Anne U and Johnson, Toby and Kleber, Marcus E and Kristiansson, Kati and Mangino, Massimo and Mateo Leach, 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  issn         = {0028-0836},
  keyword      = {Obesity: genetics,Physiologic: genetics,Neovascularization,Insulin Resistance: genetics,Insulin: metabolism,Human: genetics,Genome,Europe: ethnology,Continental Population Groups: genetics,Adipose Tissue: metabolism,Adipocytes: metabolism,Adipogenesis: genetics,Polymorphism,Single Nucleotide: genetics,Quantitative Trait Loci: genetics,Transcription,Genetic: genetics},
  language     = {eng},
  number       = {7538},
  pages        = {187--378},
  publisher    = {Nature Publishing Group},
  series       = {Nature},
  title        = {New genetic loci link adipose and insulin biology to body fat distribution.},
  url          = {http://dx.doi.org/10.1038/nature14132},
  volume       = {518},
  year         = {2015},
}