Short Communication
International Journal of Obesity (2009) 33, 284–288; doi:10.1038/ijo.2008.257; published online 9 December 2008
Common genetic variants at the MC4R locus are associated with obesity, but not with dietary energy intake or colorectal cancer in the Scottish population
A Tenesa1, H Campbell1,2, E Theodoratou1,2, L Dunlop1, R Cetnarskyj1,2,3, S M Farrington1 and M G Dunlop1
- 1Colon Cancer Genetics Group, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, University of Edinburgh, Edinburgh, UK
- 2Department of Public Health Sciences, University of Edinburgh, Edinburgh, UK
- 3Faculty of Health, Life and Social Sciences, School of Nursing, Midwifery & Social Care, Napier University, Edinburgh, UK
Correspondence: Dr A Tenesa, Colon Cancer Genetics Group, MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, 4th Floor, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU, UK. E-mail: albert.tenesa@ed.ac.uk
Received 20 July 2008; Revised 30 October 2008; Accepted 2 November 2008; Published online 9 December 2008.
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.
Keywords:
BMI, waist circumference, colon cancer, dietary energy intake, association, genetic, colorectal cancer
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