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Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits: A Multi-Ethnic Meta-Analysis of 45,891 Individuals

Author

Listed:
  • Zari Dastani
  • Marie-France Hivert
  • Nicholas Timpson
  • John R B Perry
  • Xin Yuan
  • Robert A Scott
  • Peter Henneman
  • Iris M Heid
  • Jorge R Kizer
  • Leo-Pekka Lyytikäinen
  • Christian Fuchsberger
  • Toshiko Tanaka
  • Andrew P Morris
  • Kerrin Small
  • Aaron Isaacs
  • Marian Beekman
  • Stefan Coassin
  • Kurt Lohman
  • Lu Qi
  • Stavroula Kanoni
  • James S Pankow
  • Hae-Won Uh
  • Ying Wu
  • Aurelian Bidulescu
  • Laura J Rasmussen-Torvik
  • Celia M T Greenwood
  • Martin Ladouceur
  • Jonna Grimsby
  • Alisa K Manning
  • Ching-Ti Liu
  • Jaspal Kooner
  • Vincent E Mooser
  • Peter Vollenweider
  • Karen A Kapur
  • John Chambers
  • Nicholas J Wareham
  • Claudia Langenberg
  • Rune Frants
  • Ko Willems-vanDijk
  • Ben A Oostra
  • Sara M Willems
  • Claudia Lamina
  • Thomas W Winkler
  • Bruce M Psaty
  • Russell P Tracy
  • Jennifer Brody
  • Ida Chen
  • Jorma Viikari
  • Mika Kähönen
  • Peter P Pramstaller
  • David M Evans
  • Beate St. Pourcain
  • Naveed Sattar
  • Andrew R Wood
  • Stefania Bandinelli
  • Olga D Carlson
  • Josephine M Egan
  • Stefan Böhringer
  • Diana van Heemst
  • Lyudmyla Kedenko
  • Kati Kristiansson
  • Marja-Liisa Nuotio
  • Britt-Marie Loo
  • Tamara Harris
  • Melissa Garcia
  • Alka Kanaya
  • Margot Haun
  • Norman Klopp
  • H-Erich Wichmann
  • Panos Deloukas
  • Efi Katsareli
  • David J Couper
  • Bruce B Duncan
  • Margreet Kloppenburg
  • Linda S Adair
  • Judith B Borja
  • DIAGRAM+ Consortium
  • MAGIC Consortium
  • GLGC Investigators
  • MuTHER Consortium
  • James G Wilson
  • Solomon Musani
  • Xiuqing Guo
  • Toby Johnson
  • Robert Semple
  • Tanya M Teslovich
  • Matthew A Allison
  • Susan Redline
  • Sarah G Buxbaum
  • Karen L Mohlke
  • Ingrid Meulenbelt
  • Christie M Ballantyne
  • George V Dedoussis
  • Frank B Hu
  • Yongmei Liu
  • Bernhard Paulweber
  • Timothy D Spector
  • P Eline Slagboom
  • Luigi Ferrucci
  • Antti Jula
  • Markus Perola
  • Olli Raitakari
  • Jose C Florez
  • Veikko Salomaa
  • Johan G Eriksson
  • Timothy M Frayling
  • Andrew A Hicks
  • Terho Lehtimäki
  • George Davey Smith
  • David S Siscovick
  • Florian Kronenberg
  • Cornelia van Duijn
  • Ruth J F Loos
  • Dawn M Waterworth
  • James B Meigs
  • Josee Dupuis
  • J Brent Richards

Abstract

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10−8–1.2×10−43). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p

Suggested Citation

  • Zari Dastani & Marie-France Hivert & Nicholas Timpson & John R B Perry & Xin Yuan & Robert A Scott & Peter Henneman & Iris M Heid & Jorge R Kizer & Leo-Pekka Lyytikäinen & Christian Fuchsberger & Tosh, 2012. "Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits: A Multi-Ethnic Meta-Analysis of 45,891 Individuals," PLOS Genetics, Public Library of Science, vol. 8(3), pages 1-23, March.
    • Handle: RePEc:plo:pgen00:1002607
    DOI: 10.1371/journal.pgen.1002607
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    References listed on IDEAS

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    1. Alexandra C Nica & Leopold Parts & Daniel Glass & James Nisbet & Amy Barrett & Magdalena Sekowska & Mary Travers & Simon Potter & Elin Grundberg & Kerrin Small & Åsa K Hedman & Veronique Bataille & Jo, 2011. "The Architecture of Gene Regulatory Variation across Multiple Human Tissues: The MuTHER Study," PLOS Genetics, Public Library of Science, vol. 7(2), pages 1-9, February.
    2. J Brent Richards & Dawn Waterworth & Stephen O'Rahilly & Marie-France Hivert & Ruth J F Loos & John R B Perry & Toshiko Tanaka & Nicholas John Timpson & Robert K Semple & Nicole Soranzo & Kijoung Song, 2009. "A Genome-Wide Association Study Reveals Variants in ARL15 that Influence Adiponectin Levels," PLOS Genetics, Public Library of Science, vol. 5(12), pages 1-10, December.
    3. Cecilia M Lindgren & Iris M Heid & Joshua C Randall & Claudia Lamina & Valgerdur Steinthorsdottir & Lu Qi & Elizabeth K Speliotes & Gudmar Thorleifsson & Cristen J Willer & Blanca M Herrera & Anne U J, 2009. "Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution," PLOS Genetics, Public Library of Science, vol. 5(6), pages 1-13, June.
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    Cited by:

    1. Jingjing Wu & Zheng Liu & Kai Meng & Ling Zhang, 2014. "Association of Adiponectin Gene (ADIPOQ) rs2241766 Polymorphism with Obesity in Adults: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 9(4), pages 1-9, April.
    2. Yuwei Dong & Gongping Huang & Xin Wang & Zhaoming Chu & Jingzhi Miao & Houwen Zhou, 2020. "Meta-analysis of the association between adiponectin SNP 45, SNP 276, and type 2 diabetes mellitus," PLOS ONE, Public Library of Science, vol. 15(10), pages 1-15, October.
    3. Gavin Band & Quang Si Le & Luke Jostins & Matti Pirinen & Katja Kivinen & Muminatou Jallow & Fatoumatta Sisay-Joof & Kalifa Bojang & Margaret Pinder & Giorgio Sirugo & David J Conway & Vysaul Nyirongo, 2013. "Imputation-Based Meta-Analysis of Severe Malaria in Three African Populations," PLOS Genetics, Public Library of Science, vol. 9(5), pages 1-13, May.
    4. Meng Gao & Daxia Ding & Jinghua Huang & Yali Qu & Yu Wang & Qingyang Huang, 2013. "Association of Genetic Variants in the Adiponectin Gene with Metabolic Syndrome: A Case-Control Study and a Systematic Meta-Analysis in the Chinese Population," PLOS ONE, Public Library of Science, vol. 8(4), pages 1-10, April.

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