Brief Communication | Published:

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

Nature Genetics volume 40, pages 716718 (2008) | Download Citation

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.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    & Nat. Med. 4, 1241–1243 (1998).

  2. 2.

    , & Lancet 337, 382–386 (1991).

  3. 3.

    et al. Arterioscler. Thromb. Vasc. Biol. 18, 1021–1026 (1998).

  4. 4.

    , & Diabetes Care 27, 1487–1495 (2004).

  5. 5.

    , & Lancet 365, 1415–1428 (2005).

  6. 6.

    et al. Nat. Genet. 38, 904–909 (2006).

  7. 7.

    et al. Nat. Genet. 40, 149–151 (2008).

  8. 8.

    et al. Nat. Genet. 40, 161–169 (2008).

  9. 9.

    et al. N. Engl. J. Med. 348, 1085–1095 (2003).

  10. 10.

    et al. Obesity (Silver Spring) 15, 2664–2672 (2007).

  11. 11.

    et al. Cell 123, 493–505 (2005).

  12. 12.

    et al. J. Clin. Invest. 117, 3475–3488 (2007).

  13. 13.

    & Am. J. Hum. Genet. 76, 8–32 (2005).

  14. 14.

    & Nat. Rev. Genet. 9, 179–191 (2008).

  15. 15.

    et al. Nat. Genet. 39, 1202–1207 (2007).

Download references

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

Author notes

    • 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

Authors

  1. Search for John C Chambers in:

  2. Search for Paul Elliott in:

  3. Search for Delilah Zabaneh in:

  4. Search for Weihua Zhang in:

  5. Search for Yun Li in:

  6. Search for Philippe Froguel in:

  7. Search for David Balding in:

  8. Search for James Scott in:

  9. Search for Jaspal S Kooner in:

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.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Methods, Supplementary Figures 1 and 2 and Supplementary Tables 1–7

About this article

Publication history

Received

Accepted

Published

DOI

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

Further reading