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Background  The associations between common variants in the fat mass- and obesity-associated ( FTO ) gene and obesity-related traits may be age-dependent and may differ by sex. The present study aimed to assess the association of  FTO  rs9939609 with body mass index (BMI) and the risk of obesity from childhood to adolescence, and to determine the age at which the association becomes evident.    Methods  Totally 757 obese and 2,746 non-obese Chinese children aged 6–18 years were genotyped for  FTO  rs9939609. Of these, a young sub-cohort ( n  = 777) aged 6–11 years was reexamined 6 years later. Obesity was defined using the sex- and age-specific BMI cut-offs recommended by the International Obesity Task Force.    Results  The associations of  FTO  rs9939609 with BMI and obesity did not appear until children reached 12–14 years. The variant was associated with an increased BMI in boys ( β =  1.50,  P =  0.004) and girls ( β =  0.97,  P =  0.018), respectively. Thereafter, the magnitude of association increased in girls at ages 15–18 years ( β =  2.02,  P <0.001), but not boys ( β =  0.10,  P >0.05). Age was found to interact with the variant on BMI ( P <0.001) and obesity ( P  = 0.042) only in girls. In the sub-cohort, the associations of  FTO  rs9939609 with BMI ( β =  1.07,  P =  0.008) and obesity (OR = 2.09, 95% CI: 1.12, 3.91) were only observed 6 years later (ages 12–18 years) in girls, even after adjusting for baseline BMI.    Conclusions  The association between  FTO  rs9939609 and obesity-related traits may change from childhood to adolescence in Chinese individuals, and the association may start as early as age 12 years, especially in girls.

Age- and Sex-Dependent Association between FTO rs9939609 and Obesity-Related Traits in Chinese Children and Adolescents