title: Variations in the obesity genes FTO, TMEM18 and NRXN3 influence the vulnerability of children to weight gain induced by short sleep duration.
abstract: OBJECTIVE
  Shorter sleep duration predisposes to obesity, but the mechanisms whereby sleep deprivation affects body weight are poorly understood. We tested whether this association is modulated by the obesity genes FTO, TMEM18 and NRXN3.
  
  
  METHODS
  Body mass index (BMI), waist circumference, visceral fat (abdominal ultrasound), homeostasis model assessment for insulin resistance (HOMA-IR), systolic blood pressure (SBP) and sleep time per 24 h were assessed in 297 asymptomatic children (151 boys, 146 girls; age range 5-9 years; BMI s.d. score range -2.0-4.0). Associations between sleep duration and the abovementioned outcomes were tested for three common single-nucleotide polymorphisms (SNPs), namely FTO (rs9939609), TMEM 18 (rs4854344) and NRXN3 (rs10146997), as well as for their combination.
  
  
  RESULTS
  TT homozygotes (but not A(*) carriers) for the FTO SNP, exhibited nominal associations between decreasing sleep duration and increasing BMI, waist circumference, visceral fat and HOMA-IR (all P<0.05). Similar associations were observed in children with risk alleles (but not in those without risk alleles) for the TMEM18 and NRXN3 SNPs (P<0.05 to P<0.0001). The three SNPs had additive effects on the negative associations between sleep and, respectively, BMI (P<0.001), waist (P<0.005), visceral fat (P<0.001), HOMA-IR (P=0.010) and SBP (P<0.0005). The combined effects on obesity measures and SBP remained significant after correction for multiple testing. On average, 2 h of sleep less per night was associated with an increase in BMI of 1.0 s.d. (95% confidence interval 0.5-1.6 s.d.) and with 8.0 cm (95% confidence interval 3.6-12.2 cm) more waist circumference in genetically susceptible children.
  
  
  CONCLUSIONS
  By age 7, common variations in FTO, TMEM18 and NRXN3 influence the vulnerability to metabolic complications of sleep deprivation. Further genetic studies are warranted to replicate these findings in other populations.
authors.affiliation: Pediatrics Research Group, Girona Institute for Biomedical Research, Girona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Prats-Puig
authors.forename: P
authors.initials: P
authors.lastname: Grau-Cabrera
authors.forename: E
authors.initials: E
authors.lastname: Riera-Pérez
authors.forename: R
authors.initials: R
authors.lastname: Cortés-Marina
authors.forename: E
authors.initials: E
authors.lastname: Fortea
authors.forename: P
authors.initials: P
authors.lastname: Soriano-Rodríguez
authors.forename: F
authors.initials: F
authors.lastname: de Zegher
authors.forename: L
authors.initials: L
authors.lastname: Ibánez
authors.forename: J
authors.initials: J
authors.lastname: Bassols
authors.forename: A
authors.initials: A
authors.lastname: López-Bermejo
mesh_terms: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012893:Sleep Wake Disorders / Q000235:genetics / Q000378:metabolism*; D055105:Waist Circumference; D015430:Weight Gain
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; C530715:TMEM18 protein, human; C082354:neurexin IIIalpha; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human