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

Dmitry Shungin; Thomas W. Winkler; Damien C. Croteau-Chonka; Teresa Ferreira; Adam E. Lockes; Reedik Maegi; Rona J. Strawbridge; Tune H. Pers; Krista Fischer; Anne E. Justice; Tsegaselassie Workalemahu; Joseph M. W. Wu; Martin L. Buchkovich; Nancy L. Heard-Costa; Tamara S. Roman; Alexander W. Drong; Ci Song; Stefan Gustafsson; Felix R. Day; Tonu Esko; Tove Fall; Zoltan Kutalik; Jian'an Luan; Joshua C. Randall; Andre Scherag; Rudolf Fehrmann; Juha Karjalainen; Irene Mateo Leach; Jana V. Van Vliet-Ostaptchouk; Marcel Bruinenberg; Michael R. Erdos; Catharina A. Hartman; Hans L. Hillege; Ilja M. Nolte; Salome Scholtens; Albert Vernon Smith; Morris A. Swertz; Niek Verweij; Judith M. Vonk; Jing Hua Zhao; Harm-Jan Westra; Stephan J. L. Bakker; Ron T. Gansevoort; Meena Kumari; Albertine J. Oldehinkel; Brenda W. Penninx; Ronald P. Stolk; Harold Snieder; Pim van der Harst; Lude Franke; ADIPOGen Consortium; CARDIoGRAMplusC4d Consortium; CKDGen Consortium; GEFOS Consortium; GENIE Consortium; GLGC; ICBP; Int Endogene Consortium; Lifelines Cohort Study; MAGIC Investigators; MuTHER Consortium; PAGE Consortium; ReproGen Consortium

doi:10.1038/nature14132

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

Dmitry Shungin, Thomas W. Winkler, Damien C. Croteau-Chonka, Teresa Ferreira, Adam E. Lockes, Reedik Maegi, Rona J. Strawbridge, Tune H. Pers, Krista Fischer, Anne E. Justice, Tsegaselassie Workalemahu, Joseph M. W. Wu, Martin L. Buchkovich, Nancy L. Heard-Costa, Tamara S. Roman, Alexander W. Drong, Ci Song, Stefan Gustafsson, Felix R. Day, Tonu EskoTove Fall, Zoltan Kutalik, Jian'an Luan, Joshua C. Randall, Andre Scherag, Rudolf Fehrmann, Juha Karjalainen, Irene Mateo Leach, Jana V. Van Vliet-Ostaptchouk, Marcel Bruinenberg, Michael R. Erdos, Catharina A. Hartman, Hans L. Hillege, Ilja M. Nolte, Salome Scholtens, Albert Vernon Smith, Morris A. Swertz, Niek Verweij, Judith M. Vonk, Jing Hua Zhao, Harm-Jan Westra, Stephan J. L. Bakker, Ron T. Gansevoort, Meena Kumari, Albertine J. Oldehinkel, Brenda W. Penninx, Ronald P. Stolk, Harold Snieder, Pim van der Harst, Lude Franke, ADIPOGen Consortium, CARDIoGRAMplusC4d Consortium, CKDGen Consortium, GEFOS Consortium, GENIE Consortium, GLGC, ICBP, Int Endogene Consortium, Lifelines Cohort Study, MAGIC Investigators, MuTHER Consortium, PAGE Consortium, ReproGen Consortium

Research output: Contribution to journal › Article › Academic › peer-review

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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 < 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.

Original language	English
Pages (from-to)	187-196
Number of pages	10
Journal	Nature
Volume	518
Issue number	7538
DOIs	https://doi.org/10.1038/nature14132
Publication status	Published - 12-Feb-2015

Keywords

GENOME-WIDE ASSOCIATION
MESENCHYMAL STEM-CELLS
HUMAN HEIGHT
ADIPOGENIC DIFFERENTIATION
ABDOMINAL ADIPOSITY
SUSCEPTIBILITY LOCI
SEXUAL-DIMORPHISM
GLYCEMIC TRAITS
FALSE DISCOVERY
COMMON SNPS

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New genetic loci link adipose and insulin biology to body fat distribution
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Bakker, S. (Creator), Dotinga, A. (Creator), Vonk, J. M. (Creator), Smidt, N. (Creator), Scholtens, S. (Creator), Swertz, M. (Creator), Wijmenga, C. (Creator), Wolffenbutel, B. H. (Creator), Stolk, R. (Creator), van Zon, S. (Creator), Rosmalen, J. (Creator), Postma, D. S. (Creator), de Boer, R. (Creator), Navis, G. (Creator), Slaets, J. (Creator), Ormel, J. (Creator), van Dijk, F. (Creator) & Bolmer, B. (Data Manager), Lifelines, 2006
https://www.lifelines.nl/ and one more link, https://catalogue.lifelines.nl/ (show fewer)
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Shungin, D., Winkler, T. W., Croteau-Chonka, D. C., Ferreira, T., Lockes, A. E., Maegi, R., Strawbridge, R. J., Pers, T. H., Fischer, K., Justice, A. E., Workalemahu, T., Wu, J. M. W., Buchkovich, M. L., Heard-Costa, N. L., Roman, T. S., Drong, A. W., Song, C., Gustafsson, S., Day, F. R., ... ReproGen Consortium (2015). New genetic loci link adipose and insulin biology to body fat distribution. Nature, 518(7538), 187-196. https://doi.org/10.1038/nature14132

@article{52b2bd398213480c8405e737388f3bb8,

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, 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.",

keywords = "GENOME-WIDE ASSOCIATION, MESENCHYMAL STEM-CELLS, HUMAN HEIGHT, ADIPOGENIC DIFFERENTIATION, ABDOMINAL ADIPOSITY, SUSCEPTIBILITY LOCI, SEXUAL-DIMORPHISM, GLYCEMIC TRAITS, FALSE DISCOVERY, COMMON SNPS",

author = "Dmitry Shungin and Winkler, {Thomas W.} and Croteau-Chonka, {Damien C.} and Teresa Ferreira and Lockes, {Adam E.} and Reedik Maegi and Strawbridge, {Rona J.} and Pers, {Tune H.} and Krista Fischer and Justice, {Anne E.} and Tsegaselassie Workalemahu and Wu, {Joseph M. W.} and Buchkovich, {Martin L.} and Heard-Costa, {Nancy L.} and Roman, {Tamara S.} and Drong, {Alexander W.} and Ci Song and Stefan Gustafsson and Day, {Felix R.} and Tonu Esko and Tove Fall and Zoltan Kutalik and Jian'an Luan and Randall, {Joshua C.} and Andre Scherag and Rudolf Fehrmann and Juha Karjalainen and Leach, {Irene Mateo} and {Van Vliet-Ostaptchouk}, {Jana V.} and Marcel Bruinenberg and Erdos, {Michael R.} and Hartman, {Catharina A.} and Hillege, {Hans L.} and Nolte, {Ilja M.} and Salome Scholtens and Smith, {Albert Vernon} and Swertz, {Morris A.} and Niek Verweij and Vonk, {Judith M.} and Zhao, {Jing Hua} and Harm-Jan Westra and Bakker, {Stephan J. L.} and Gansevoort, {Ron T.} and Meena Kumari and Oldehinkel, {Albertine J.} and Penninx, {Brenda W.} and Stolk, {Ronald P.} and Harold Snieder and {van der Harst}, Pim and Lude Franke and {ADIPOGen Consortium} and {CARDIoGRAMplusC4d Consortium} and {CKDGen Consortium} and {GEFOS Consortium} and {GENIE Consortium} and GLGC and ICBP and {Int Endogene Consortium} and {Lifelines Cohort Study} and {MAGIC Investigators} and {MuTHER Consortium} and {PAGE Consortium} and {ReproGen Consortium}",

year = "2015",

month = feb,

day = "12",

doi = "10.1038/nature14132",

language = "English",

volume = "518",

pages = "187--196",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "7538",

}

Shungin, D, Winkler, TW, Croteau-Chonka, DC, Ferreira, T, Lockes, AE, Maegi, R, Strawbridge, RJ, Pers, TH, Fischer, K, Justice, AE, Workalemahu, T, Wu, JMW, Buchkovich, ML, Heard-Costa, NL, Roman, TS, Drong, AW, Song, C, Gustafsson, S, Day, FR, Esko, T, Fall, T, Kutalik, Z, Luan, J, Randall, JC, Scherag, A, Fehrmann, R, Karjalainen, J, Leach, IM , Van Vliet-Ostaptchouk, JV , Bruinenberg, M, Erdos, MR, Hartman, CA , Hillege, HL , Nolte, IM , Scholtens, S, Smith, AV, Swertz, MA, Verweij, N, Vonk, JM, Zhao, JH, Westra, H-J , Bakker, SJL , Gansevoort, RT, Kumari, M, Oldehinkel, AJ, Penninx, BW, Stolk, RP , Snieder, H , van der Harst, P , Franke, L, ADIPOGen Consortium, CARDIoGRAMplusC4d Consortium, CKDGen Consortium, GEFOS Consortium, GENIE Consortium, GLGC, ICBP, Int Endogene Consortium, Lifelines Cohort Study, MAGIC Investigators, MuTHER Consortium, PAGE Consortium & ReproGen Consortium 2015, 'New genetic loci link adipose and insulin biology to body fat distribution', Nature, vol. 518, no. 7538, pp. 187-196. https://doi.org/10.1038/nature14132

TY - JOUR

T1 - New genetic loci link adipose and insulin biology to body fat distribution

AU - Shungin, Dmitry

AU - Winkler, Thomas W.

AU - Croteau-Chonka, Damien C.

AU - Ferreira, Teresa

AU - Lockes, Adam E.

AU - Maegi, Reedik

AU - Strawbridge, Rona J.

AU - Pers, Tune H.

AU - Fischer, Krista

AU - Justice, Anne E.

AU - Workalemahu, Tsegaselassie

AU - Wu, Joseph M. W.

AU - Buchkovich, Martin L.

AU - Heard-Costa, Nancy L.

AU - Roman, Tamara S.

AU - Drong, Alexander W.

AU - Song, Ci

AU - Gustafsson, Stefan

AU - Day, Felix R.

AU - Esko, Tonu

AU - Fall, Tove

AU - Kutalik, Zoltan

AU - Luan, Jian'an

AU - Randall, Joshua C.

AU - Scherag, Andre

AU - Fehrmann, Rudolf

AU - Karjalainen, Juha

AU - Leach, Irene Mateo

AU - Van Vliet-Ostaptchouk, Jana V.

AU - Bruinenberg, Marcel

AU - Erdos, Michael R.

AU - Hartman, Catharina A.

AU - Hillege, Hans L.

AU - Nolte, Ilja M.

AU - Scholtens, Salome

AU - Smith, Albert Vernon

AU - Swertz, Morris A.

AU - Verweij, Niek

AU - Vonk, Judith M.

AU - Zhao, Jing Hua

AU - Westra, Harm-Jan

AU - Bakker, Stephan J. L.

AU - Gansevoort, Ron T.

AU - Kumari, Meena

AU - Oldehinkel, Albertine J.

AU - Penninx, Brenda W.

AU - Stolk, Ronald P.

AU - Snieder, Harold

AU - van der Harst, Pim

AU - Franke, Lude

AU - ADIPOGen Consortium

AU - CARDIoGRAMplusC4d Consortium

AU - CKDGen Consortium

AU - GEFOS Consortium

AU - GENIE Consortium

AU - GLGC

AU - ICBP

AU - Int Endogene Consortium

AU - Lifelines Cohort Study

AU - MAGIC Investigators

AU - MuTHER Consortium

AU - PAGE Consortium

AU - ReproGen Consortium

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, 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.

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, 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.

KW - GENOME-WIDE ASSOCIATION

KW - MESENCHYMAL STEM-CELLS

KW - HUMAN HEIGHT

KW - ADIPOGENIC DIFFERENTIATION

KW - ABDOMINAL ADIPOSITY

KW - SUSCEPTIBILITY LOCI

KW - SEXUAL-DIMORPHISM

KW - GLYCEMIC TRAITS

KW - FALSE DISCOVERY

KW - COMMON SNPS

U2 - 10.1038/nature14132

DO - 10.1038/nature14132

M3 - Article

C2 - 25673412

SN - 0028-0836

VL - 518

SP - 187

EP - 196

JO - Nature

JF - Nature

IS - 7538

ER -

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

Abstract

Keywords

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