title: Non-replication of genome-wide based associations between common variants in INSIG2 and PFKP and obesity in studies of 18,014 Danes.
abstract: BACKGROUND
  The INSIG2 rs7566605 and PFKP rs6602024 polymorphisms have been identified as obesity gene variants in genome-wide association (GWA) studies. However, replication has been contradictory for both variants. The aims of this study were to validate these obesity-associations through case-control studies and analyses of obesity-related quantitative traits. Moreover, since environmental and genetic factors may modulate the impact of a genetic variant, we wanted to perform such interaction analyses. We focused on physical activity as an environmental risk factor, and on the GWA identified obesity variants in FTO (rs9939609) and near MC4R (rs17782313) as genetic risk factors.
  
  
  METHODS
  The four variants were genotyped in a combined study sample comprising a total of 18,014 subject ascertained from, the population-based Inter99 cohort (n = 6,514), the ADDITION screening cohort (n = 8,662), a population-based study sample (n = 680) and a type 2 diabetic patient group (n = 2,158) from Steno Diabetes Center.
  
  
  RESULTS
  No association with overweight, obesity or obesity-related measures was shown for either the INSIG2 rs7566605 or the PFKP rs6602024 variants. However, an interaction between the INSIG2 rs7566605 variant and the level of self-reported physical activity (p(Int) = 0.004) was observed. A BMI difference of 0.53 (SE 0.42) kg/m(2) was found when comparing physically passive homozygous C-allele carriers with physically passive G-allele carriers. No interactions between the two variants and FTO rs9939609 and MC4R rs17782313 were observed.
  
  
  CONCLUSIONS
  The INSIG2 rs7566605 and PFKP rs6602024 polymorphisms play no apparent role in the development of common forms of obesity in the Danish population. However, if replicated, the INSIG2 rs7566605 may influence the level of BMI in combination with the level of physical activity.
authors.affiliation: Steno Diabetes Center, Copenhagen, Denmark.
authors.forename: Camilla H
authors.initials: CH
authors.lastname: Andreasen
authors.forename: Mette S
authors.initials: MS
authors.lastname: Mogensen
authors.forename: Knut
authors.initials: K
authors.lastname: Borch-Johnsen
authors.forename: Annelli
authors.initials: A
authors.lastname: Sandbaek
authors.forename: Torsten
authors.initials: T
authors.lastname: Lauritzen
authors.forename: Thorkild I A
authors.initials: TI
authors.lastname: Sørensen
authors.forename: Lars
authors.initials: L
authors.lastname: Hansen
authors.forename: Katrine
authors.initials: K
authors.lastname: Almind
authors.forename: Torben
authors.initials: T
authors.lastname: Jørgensen
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
mesh_terms: D001792:Blood Platelets / Q000201:enzymology; D004261:DNA Replication; D003718:Denmark; D015444:Exercise; D005260:Female; D014644:Genetic Variation; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009043:Motor Activity; D009765:Obesity / Q000235:genetics*; D050177:Overweight / Q000235:genetics; D025221:Phosphofructokinases / Q000097:blood / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: C467727:INSIG2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D025221:Phosphofructokinases