title: Lack of association between DRD2 and OPRM1 genotypes and adiposity.
abstract: BACKGROUND
  Dopaminergic and opioid systems are both involved in food intake and appetite control. The dopamine D2 receptor gene (DRD2) and the μ-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.
  
  
  METHODS
  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 per-allele 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 kg m(-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychological Sciences, University of Liverpool, Liverpool, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: Hardman
authors.affiliation: School of Experimental Psychology, University of Bristol, Bristol, UK.
authors.forename: P J
authors.initials: PJ
authors.lastname: Rogers
authors.affiliation: MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK.
authors.forename: N J
authors.initials: NJ
authors.lastname: Timpson
authors.affiliation: MRC Integrative Epidemiology Unit, UK Centre for Tobacco and Alcohol Studies and School of Experimental Psychology, University of Bristol, Bristol, UK.
authors.forename: M R
authors.identifier: 000000024049993X
authors.initials: MR
authors.lastname: Munafò
mesh_terms: D050154:Adiposity / Q000235:genetics*; D000328:Adult; D000483:Alleles; D001069:Appetite Regulation / Q000235:genetics*; D015992:Body Mass Index; D002648:Child; D004435:Eating / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D011247:Pregnancy; D017448:Receptors, Dopamine D2; D017450:Receptors, Opioid, mu
chemical_list: C581293:DRD2 protein, human; C485764:OPRM1 protein, human; D017448:Receptors, Dopamine D2; D017450:Receptors, Opioid, mu
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