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Common genetic variation near MC4R is associated with waist circumference and insulin resistance

Nature Genetics volume 40, pages 716–718 (2008)Cite this article

Abstract

We carried out a genome-wide association study (318,237 SNPs) for insulin resistance and related phenotypes in 2,684 Indian Asians, with further testing in 11,955 individuals of Indian Asian or European ancestry. We found associations of rs12970134 near MC4R with waist circumference (P = 1.7 × 10−9) and, independently, with insulin resistance. Homozygotes for the risk allele of rs12970134 have ∼2 cm increased waist circumference. Common genetic variation near MC4R is associated with risk of adiposity and insulin resistance.

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Acknowledgements

At Ealing Hospital and Imperial College, we thank J. Wrigley, S. Trainor and the team of research nurses for subject characterization and sample handling; and C. Hoggart, R. Walters, X. Li and P. Thomason (supported by Wellcome Trust grant 066786) for assistance with data analysis. The work was supported by the British Heart Foundation Grant SP/04/002.

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Author notes

  1. John C Chambers and Paul Elliott: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Epidemiology and Public Health, Imperial College London, Norfolk Pl., W2 1PG, London, UK

    John C Chambers, Paul Elliott, Delilah Zabaneh, Weihua Zhang & David Balding

  2. Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, Michigan, USA

    Yun Li

  3. Section of Genomic Medicine, Imperial College London, Hammersmith Hospital, Du Cane Rd., London, W12 0NN, UK

    Philippe Froguel

  4. Centre National de la Recherche Scientifique, 8090-Institute of Biology, Pasteur Institute, Lille, France

    Philippe Froguel

  5. National Heart and Lung Institute, Imperial College London Hammersmith Hospital, Du Cane Rd., London, W12 0NN, UK

    James Scott & Jaspal S Kooner

Authors
  1. John C Chambers
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  2. Paul Elliott
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  3. Delilah Zabaneh
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  4. Weihua Zhang
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  5. Yun Li
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  6. Philippe Froguel
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  7. David Balding
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  8. James Scott
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  9. Jaspal S Kooner
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Contributions

J.C.C., P.E., D.Z., D.B., J.S., P.F. and J.S.K. designed the study. J.C.C., P.E. and J.S.K. supervised recruitment of study subjects. D.Z., J.C.C., P.E., J.S. and J.S.K. supervised the experiments. J.C.C., D.Z., W.Z., Y.L. and D.B. performed data analysis. J.C.C., P.E., J.S. and J.S.K. wrote the manuscript. All authors commented on and approved the manuscript.

Corresponding author

Correspondence to Jaspal S Kooner.

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Supplementary Methods, Supplementary Figures 1 and 2 and Supplementary Tables 1–7 (PDF 278 kb)

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Chambers, J., Elliott, P., Zabaneh, D. et al. Common genetic variation near MC4R is associated with waist circumference and insulin resistance. Nat Genet 40, 716–718 (2008). https://doi.org/10.1038/ng.156

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