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Variations in the obesity genes FTO, TMEM18 and NRXN3 influence the vulnerability of children to weight gain induced by short sleep duration



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.


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.


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.


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.

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We are grateful to all the children and parents who took part in this study. FdZ is a Senior Investigator of the Clinical Research Fund of the Leuven University Hospital, Belgium. LI is a Clinical Investigator of the CIBERDEM (Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders), from the National Institute of Health Carlos III, Spain. JB is an Investigator of the Sara Borrell Fund from the National Institute of Health Carlos III, Spain. AL-B is an Investigator of the I3 Fund for Scientific Research (Ministry of Science and Innovation, Spain). This work was supported, in part, by grant 10/00553 (to AL-B) from the National Institute of Health Carlos III (Fund for Health Research FIS, Spain).

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Correspondence to A López-Bermejo.

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Prats-Puig, A., Grau-Cabrera, P., Riera-Pérez, E. et al. Variations in the obesity genes FTO, TMEM18 and NRXN3 influence the vulnerability of children to weight gain induced by short sleep duration. Int J Obes 37, 182–187 (2013).

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  • FTO
  • TMEM18
  • NRXN3
  • sleep
  • BMI
  • children

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