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

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 . SUBJECTS: 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