Sex modifies the association between the CLOCK variant rs1801260 and BMI in school-age children

Disruption of circadian rhythms and variations in the FTO gene may interfere with energy homeostasis and play a role in the development of obesity. The current study assessed the association of common polymorphisms in the CLOCK and FTO genes with standardized body mass index scores (BMI z-scores) and their potential modification of the impact of a culinary nutrition and physical activity intervention in school-age children. Anthropometric measurements were collected in 121 children at the baseline and one-year follow-up of a controlled trial of a school-based culinary nutrition and physical activity intervention. Genotypes of the CLOCK polymorphism (rs1801260) and the FTO polymorphism (rs9939609) were obtained from buccal swabs. Linear mixed-effects regression was applied to evaluate the genetic association and adjust for clusters within families and schools. In our participants, obesity affected 6.6% (8/121) of the children at the baseline and 6.4% (7/109) of the children at the follow-up. The associations between the age- and sex-adjusted BMI z-scores and the two polymorphisms did not reach statistically significance. Yet, sex potentially modified the association between rs1801260 and BMI z-scores. In girls, the G allele carriers had a higher BMI z-scores at the baseline and the follow-up. These polymorphisms did not modify the effect of our culinary nutrition and physical activity intervention on BMI z-scores. Sex is a potential modifier for the association between the CLOCK polymorphism, rs1801260, and BMI z-scores in school-age children. Further investigation is warranted to delineate the sex-dependent role of the CLOCK polymorphisms in the development of childhood obesity.