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Common genetic variants at the MC4R locus are associated with obesity, but not with dietary energy intake or colorectal cancer in the Scottish population

International Journal of Obesity volume 33, pages 284–288 (2009)Cite this article

Abstract

Background:

Common single-nucleotide polymorphism (SNP) variants around the melanocortin 4 receptor (MC4R) gene have recently been associated with obesity risk and insulin resistance. Obesity is a known risk factor for colorectal cancer (CRC) and we hypothesized that there might be a common inherited genetic component.

Methods and Results:

Four of the variants reported earlier were genotyped and tested for association with body mass index (BMI), waist circumference (WC), dietary energy intake (DEI) and CRC. Using a case–control genetic association study, we replicated the association with BMI (P=0.0001, additive genetic effect=0.37 kg/m2) and WC (P=0.005, additive genetic effect=0.70 cm) using over 3800 individuals. However, there was no association between these variants and CRC risk. Rare (highly penetrant) variants within the MC4R gene have been shown to influence eating behaviour and hyperphagia. We hypothesized that the newly identified common variants might also influence hyperphagia. Using DEI data recorded from a validated food frequency questionnaire, we found no significant genetic association between MC4R SNPs and DEI.

Conclusions:

As the MC4R locus explains only 0.28% of the BMI and 0.14% of the WC phenotypic variance in the Scottish population, most of the genetic contribution to obesity remains to be identified.

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Acknowledgements

We are grateful to all participants in these studies and to nursing and administrative staff on the COGS and SOCCS studies. We also thank departments in central Scottish NHS, including Cancer Registry, Scottish Cancer Intelligence Unit of ISD and the Family Practitioner Committee. This study was funded by grants from Cancer Research UK (C348/A3758 and -A8896, C48/A6361); Medical Research Council (G0000657-53203); Scottish Executive Chief Scientist's Office (K/OPR/2/2/D333, CZB/4/449); and Centre Grant from CORE as part of the Digestive Cancer Campaign (http://www.corecharity.org.uk).

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Authors and Affiliations

  1. Colon Cancer Genetics Group, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, UK

    A Tenesa, H Campbell, E Theodoratou, L Dunlop, R Cetnarskyj, S M Farrington & M G Dunlop

  2. Department of Public Health Sciences, University of Edinburgh, Edinburgh, UK

    H Campbell, E Theodoratou & R Cetnarskyj

  3. Faculty of Health, Life and Social Sciences, School of Nursing, Midwifery & Social Care, Napier University, Edinburgh, UK

    R Cetnarskyj

Authors
  1. A Tenesa
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  2. H Campbell
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  3. E Theodoratou
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  4. L Dunlop
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  5. R Cetnarskyj
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  6. S M Farrington
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  7. M G Dunlop
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Corresponding author

Correspondence to A Tenesa.

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Tenesa, A., Campbell, H., Theodoratou, E. et al. Common genetic variants at the MC4R locus are associated with obesity, but not with dietary energy intake or colorectal cancer in the Scottish population. Int J Obes 33, 284–288 (2009). https://doi.org/10.1038/ijo.2008.257

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