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

doi:10.1038/nature14132

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

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1317 Citas (SciVal)

Resumen

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, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10^-8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed 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.

Idioma original	English
Páginas (desde-hasta)	187-196
Número de páginas	10
Publicación	Nature
Volumen	518
N.º	7538
DOI	https://doi.org/10.1038/nature14132
Estado	Published - feb 12 2015

Nota bibliográfica

Publisher Copyright:
© 2015, Macmillan Publishers Limited. All rights reserved.

Financiación

Financiadores	Número del financiador
National Institutes of Health (NIH)	U01HG007376, R01AG041517, U01HG007416, P30DK072488, R01HL117078, P30DK020541, K23DK080145
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases	P30DK079637
National Institute of Diabetes and Digestive and Kidney Diseases

ASJC Scopus subject areas

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@article{2566499fa89d4efa8f88c2cabf0fd52c,

title = "New genetic loci link adipose and insulin biology to body fat distribution",

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, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10-8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed 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 = "D. Shungin and Winkler, \{T. W.\} and Croteau-Chonka, \{D. C.\} and T. Ferreira and Locke, \{A. E.\} and R. M{\"a}gi and Strawbridge, \{R. J.\} and Pers, \{T. H.\} and K. Fischer and Justice, \{A. E.\} and T. Workalemahu and Wu, \{J. M.W.\} and Buchkovich, \{M. L.\} and Heard-Costa, \{N. L.\} and Roman, \{T. S.\} and Drong, \{A. W.\} and C. Song and S. Gustafsson and Day, \{F. R.\} and T. Esko and T. Fall and Z. Kutalik and J. Luan and Randall, \{J. C.\} and A. Scherag and S. Vedantam and Wood, \{A. R.\} and J. Chen and R. Fehrmann and J. Karjalainen and B. Kahali and Liu, \{C. T.\} and Schmidt, \{E. M.\} and D. Absher and N. Amin and D. Anderson and M. Beekman and Bragg-Gresham, \{J. L.\} and S. Buyske and A. Demirkan and Ehret, \{G. B.\} and Feitosa, \{M. F.\} and A. Goel and Jackson, \{A. U.\} and T. Johnson and Kleber, \{M. E.\} and K. Kristiansson and M. Mangino and Leach, \{I. M.\} and C. He",

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AU - Winkler, T. W.

AU - Croteau-Chonka, D. C.

AU - Ferreira, T.

AU - Locke, A. E.

AU - Mägi, R.

AU - Strawbridge, R. J.

AU - Pers, T. H.

AU - Fischer, K.

AU - Justice, A. E.

AU - Workalemahu, T.

AU - Wu, J. M.W.

AU - Buchkovich, M. L.

AU - Heard-Costa, N. L.

AU - Roman, T. S.

AU - Drong, A. W.

AU - Song, C.

AU - Gustafsson, S.

AU - Day, F. R.

AU - Esko, T.

AU - Fall, T.

AU - Kutalik, Z.

AU - Luan, J.

AU - Randall, J. C.

AU - Scherag, A.

AU - Vedantam, S.

AU - Wood, A. R.

AU - Chen, J.

AU - Fehrmann, R.

AU - Karjalainen, J.

AU - Kahali, B.

AU - Liu, C. T.

AU - Schmidt, E. M.

AU - Absher, D.

AU - Amin, N.

AU - Anderson, D.

AU - Beekman, M.

AU - Bragg-Gresham, J. L.

AU - Buyske, S.

AU - Demirkan, A.

AU - Ehret, G. B.

AU - Feitosa, M. F.

AU - Goel, A.

AU - Jackson, A. U.

AU - Johnson, T.

AU - Kleber, M. E.

AU - Kristiansson, K.

AU - Mangino, M.

AU - Leach, I. M.

AU - He, C.

PY - 2015/2/12

Y1 - 2015/2/12

N2 - 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, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10-8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed 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.

AB - 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, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10-8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed 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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VL - 518

SP - 187

EP - 196

JO - Nature

JF - Nature

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ER -

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

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