Lack of association between DRD2 and OPRM1 genotypes and adiposity

C. A. Hardman*, P. J. Rogers, N. J. Timpson, M. R. Munafo

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

23 Citations (Scopus)

Abstract

BACKGROUND: Dopaminergic and opioid systems are both involved in food intake and appetite control. The dopamine D2 receptor gene (DRD2) and the m-opioid receptor gene (OPRM1) therefore represent plausible candidates for association with obesity.

OBJECTIVE: Previous studies of these variants have yielded inconsistent findings, which are likely due to insufficient statistical power. The aim of the current study was to determine whether, in a large population-based sample, there are associations between adiposity and (i) the A1 (T) allele of the Taq1A polymorphism (rs1800497) in DRD2 and (ii) the G allele of the A118G polymorphism (rs1799971) in OPRM1.

STUDY POPULATION: Annual clinic-based measures of body mass index (BMI) and waist circumference were taken from children (N = 3720) at 5 measurement time points from ages 7 through to 11 years. BMI was also recorded in their mothers (N = 2460) at comparable time points and at pre-pregnancy. All participants were genotyped. Our study was powered (at 80%) to detect perallele effects on BMI of 0.21 kg m(-2).

RESULTS: Our results indicate a lack of association between DRD2 and OPRM1 genotypes and adiposity. Combining the data across mothers and children found per-allele effects on BMI of 0.02 kgm (-2) (95% confidence interval (CI): -0.17, 0.20), P = 0.9 for rs1800497 and 0.08 kg m(-2) (95% CI: 0.29, 0.22), P = 0.4 for rs1799971. As a positive control, we also examined the effect of FTO genotype over the same time period and confirmed the expected relationship between variability at this locus and higher adiposity.

CONCLUSION: Our findings question existing evidence suggesting associations at DRD2 and OPRM1 loci and adiposity. They also highlight the caution required when employing candidate gene approaches to further our understanding of the neurobiology of eating and obesity.

Original languageEnglish
Pages (from-to)730-736
Number of pages7
JournalInternational Journal of Obesity
Volume38
Issue number5
DOIs
Publication statusPublished - 6 Aug 2013

Structured keywords

  • Brain and Behaviour
  • Tobacco and Alcohol
  • Nutrition and Behaviour

Keywords

  • dopamine
  • opioids
  • candidate genes
  • ALSPAC
  • GENOME-WIDE ASSOCIATION
  • DOPAMINE-RECEPTOR GENE
  • BODY-MASS INDEX
  • D2 RECEPTOR
  • MENDELIAN RANDOMIZATION
  • HEALTHY-VOLUNTEERS
  • FAT DISTRIBUTION
  • COMMON DISEASES
  • BLOOD-PRESSURE
  • A1 ALLELE

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