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.
This is a preview of subscription content, access via your institution
Access options
Similar content being viewed by others
References
Lopez, A.D. & Murray, C.C. Nat. Med. 4, 1241–1243 (1998).
McKeigue, P.M., Shah, B. & Marmot, M.G. Lancet 337, 382–386 (1991).
Kooner, J.S. et al. Arterioscler. Thromb. Vasc. Biol. 18, 1021–1026 (1998).
Wallace, T.M., Levy, J.C. & Matthews, D.R. Diabetes Care 27, 1487–1495 (2004).
Eckel, R.H., Grundy, S.M. & Zimmet, P.Z. Lancet 365, 1415–1428 (2005).
Price, A.L. et al. Nat. Genet. 38, 904–909 (2006).
Kooner, J.S. et al. Nat. Genet. 40, 149–151 (2008).
Willer, C.J. et al. Nat. Genet. 40, 161–169 (2008).
Farooqi, I.S. et al. N. Engl. J. Med. 348, 1085–1095 (2003).
Trevaskis, J.L. et al. Obesity (Silver Spring) 15, 2664–2672 (2007).
Balthasar, N. et al. Cell 123, 493–505 (2005).
Nogueiras, R. et al. J. Clin. Invest. 117, 3475–3488 (2007).
Kleinjan, D.A. & van Heyningen, V. Am. J. Hum. Genet. 76, 8–32 (2005).
Schones, D.E. & Zhao, K. Nat. Rev. Genet. 9, 179–191 (2008).
Dixon, A.L. et al. Nat. Genet. 39, 1202–1207 (2007).
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
Authors and Affiliations
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
Supplementary information
Supplementary Text and Figures
Supplementary Methods, Supplementary Figures 1 and 2 and Supplementary Tables 1–7 (PDF 278 kb)
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ng.156
This article is cited by
-
The relationship of genetic risk score with cardiometabolic risk factors: a cross-sectional study
BMC Cardiovascular Disorders (2022)
-
Transferability of genetic loci and polygenic scores for cardiometabolic traits in British Pakistani and Bangladeshi individuals
Nature Communications (2022)
-
The genetics of obesity: from discovery to biology
Nature Reviews Genetics (2022)
-
Genomics of body fat distribution
Journal of Genetics (2021)
-
Dietary quality indices modifies the effects of melanocortin-4 receptor (MC4R) rs17782313 polymorphism on cardio-metabolic risk factors and hypothalamic hormones in obese adults
BMC Cardiovascular Disorders (2020)