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

Nature Genetics 40, 716–718 (2008) | Download Citation

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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.

Author information

    • John C Chambers
    •  & Paul Elliott

    These authors contributed equally to this work.

Affiliations

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

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

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

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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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DOI

https://doi.org/10.1038/ng.156

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