title: Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples.
abstract: BACKGROUND
  Meta-analysis of case-control genome-wide association studies (GWAS) for early onset and morbid obesity identified four variants in/near the PRL, PTER, MAF and NPC1 genes.
  
  
  OBJECTIVE
  We aimed to validate association of these variants with obesity-related traits in population-based samples.
  
  
  METHODS
  Genotypes and anthropometric traits were available in up to 31 083 adults from the Fenland, EPIC-Norfolk, Whitehall II, Ely and Hertfordshire studies and in 2042 children and adolescents from the European Youth Heart Study. In each study, we tested associations of rs4712652 (near-PRL), rs10508503 (near-PTER), rs1424233 (near-MAF) and rs1805081 (NPC1), or proxy variants (r (2)>0.8), with the odds of being overweight and obese, as well as with body mass index (BMI), percentage body fat (%BF) and waist circumference (WC). Associations were adjusted for sex, age and age(2) in adults and for sex, age, age group, country and maturity in children and adolescents. Summary statistics were combined using fixed effects meta-analysis methods.
  
  
  RESULTS
  We had 80% power to detect odds ratios of 1.046 to 1.092 for overweight and 1.067 to 1.136 for obesity. Variants near PRL, PTER and MAF were not associated with the odds of being overweight or obese, or with BMI, %BF or WC after meta-analysis (P>0.15). The NPC1 variant rs1805081 showed some evidence of association with %BF (β=0.013 s.d./allele, P=0.040), but not with any of the remaining obesity-related traits (P>0.3).
  
  
  CONCLUSIONS
  Overall, these variants, which were identified in a GWAS for early onset and morbid obesity, do not seem to influence obesity-related traits in the general population.
authors.affiliation: MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: M
authors.initials: M
authors.lastname: den Hoed
authors.forename: J
authors.initials: J
authors.lastname: Luan
authors.forename: C
authors.initials: C
authors.lastname: Langenberg
authors.forename: C
authors.initials: C
authors.lastname: Cooper
authors.forename: A A
authors.initials: AA
authors.lastname: Sayer
authors.forename: K
authors.initials: K
authors.lastname: Jameson
authors.forename: M
authors.initials: M
authors.lastname: Kumari
authors.forename: M
authors.initials: M
authors.lastname: Kivimaki
authors.forename: A D
authors.initials: AD
authors.lastname: Hingorani
authors.forename: A
authors.initials: A
authors.lastname: Grøntved
authors.forename: K-T
authors.initials: KT
authors.lastname: Khaw
authors.forename: U
authors.initials: U
authors.lastname: Ekelund
authors.forename: N J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: R J F
authors.initials: RJ
authors.lastname: Loos
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015992:Body Mass Index; D002352:Carrier Proteins / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D004739:England / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D000077296:Niemann-Pick C1 Protein; D009767:Obesity, Morbid / Q000453:epidemiology* / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011388:Prolactin / Q000235:genetics; D051257:Proto-Oncogene Proteins c-maf / Q000235:genetics; D055105:Waist Circumference; D044465:White People / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C495607:MAF protein, human; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; C484578:PTER protein, human; D051257:Proto-Oncogene Proteins c-maf; D011388:Prolactin