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


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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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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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.

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Correspondence to Jaspal S Kooner.

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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).

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