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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Heid, Iris M.; Jackson, Anne U.; Randall, Joshua C.; Winkler, Thomas W.; Qi, Lu; Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Zillikens, M. Carola; Speliotes, Elizabeth K. and Maegi, Reedik, et al. (2010) In Nature Genetics 42(11). p.160-949
Abstract
Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 x 10(-9) to P = 1.8 x 10(-40)) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all... (More)
Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 x 10(-9) to P = 1.8 x 10(-40)) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 x 10(-3) to P = 1.2 x 10(-13)). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions. (Less)
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Nature Genetics
volume
42
issue
11
pages
160 - 949
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Nature Publishing Group
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  • wos:000283540500011
  • scopus:78049349396
ISSN
1546-1718
DOI
10.1038/ng.685
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English
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yes
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46e5515c-d766-40ce-8cc4-6ea53a2a0262 (old id 1719319)
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2010-12-23 09:47:40
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  abstract     = {Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 x 10(-9) to P = 1.8 x 10(-40)) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 x 10(-3) to P = 1.2 x 10(-13)). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.},
  author       = {Heid, Iris M. and Jackson, Anne U. and Randall, Joshua C. and Winkler, Thomas W. and Qi, Lu and Steinthorsdottir, Valgerdur and Thorleifsson, Gudmar and Zillikens, M. Carola and Speliotes, Elizabeth K. and Maegi, Reedik and Workalemahu, Tsegaselassie and White, Charles C. and Bouatia-Naji, Nabila and Harris, Tamara B. and Berndt, Sonja I. and Ingelsson, Erik and Willer, Cristen J. and Weedon, Michael N. and Luan, Jianan and Vedantam, Sailaja and Esko, Tonu and Kilpelaeinen, Tuomas O. and Kutalik, Zoltan and Li, Shengxu and Monda, Keri L. and Dixon, Anna L. and Holmes, Christopher C. and Kaplan, Lee M. and Liang, Liming and Min, Josine L. and Moffatt, Miriam F. and Molony, Cliona and Nicholson, George and Schadt, Eric E. and Zondervan, Krina T. and Feitosa, Mary F. and Ferreira, Teresa and Allen, Hana Lango and Weyant, Robert J. and Wheeler, Eleanor and Wood, Andrew R. and Estrada, Karol and Goddard, Michael E. and Lettre, Guillaume and Mangino, Massimo and Nyholt, Dale R. and Purcell, Shaun and Smith, Albert Vernon and Visscher, Peter M. and Yang, Jian and McCarroll, Steven A. and Nemesh, James and Voight, Benjamin F. and Absher, Devin and Amin, Najaf and Aspelund, Thor and Coin, Lachlan and Glazer, Nicole L. and Hayward, Caroline and Heard-Costa, Nancy L. and Hottenga, Jouke-Jan and Johansson, Asa and Johnson, Toby and Kaakinen, Marika and Kapur, Karen and Ketkar, Shamika and Knowles, Joshua W. and Kraft, Peter and Kraja, Aldi T. and Lamina, Claudia and Leitzmann, Michael F. and McKnight, Barbara and Morris, Andrew P. and Ong, Ken K. and Perry, John R. 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  issn         = {1546-1718},
  language     = {eng},
  number       = {11},
  pages        = {160--949},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution},
  url          = {http://dx.doi.org/10.1038/ng.685},
  volume       = {42},
  year         = {2010},
}