Background: The influence of single nucleotide polymorphisms (SNP) of the FTO gene has been shown to change over time. Objective: The aim was to investigate the relationship between a SNP of the FTO gene (rs9939609) and obesity-related characteristics longitudinally during childhood and puberty. Design: From 101 children (58 boys and 43 girls), the FTO (rs9939609) genotype and yearly anthropometric data from birth to age 7 yr were determined. From ages 12 to 17 yr, we measured anthropometry, body composition, leptin concentrations, physical activity, hours watching television, and attitude toward eating yearly; parental characteristics were determined as well. Results: At age 17 yr, 20% of the children were overweight/obese, and 88% of the overweight/obese children had the A allele in contrast to 45% of the lean children (P < 0.001). The A allele carriers had a higher fat mass index (kilograms per square meter) and higher leptin concentrations (micrograms per liter) during puberty, except at age 14 yr. Multiple regression analyses with body mass index (BMI; kilograms per square meter) as the dependent variable showed that at ages 12 and 17 yr, dietary restraint score, disinhibition score, BMI of the mother, and the FTO A allele significantly contributed to the model (R(2) = 0.29, P < 0.002; and R(2) = 0.39, P < 0.001). At age 14 yr, dietary restraint score, disinhibition score, and leptin concentrations per kilogram of fat mass significantly contributed to the model (R(2) = 0.25; P < 0.02). Conclusion: The FTO A allele (rs9939609) is associated with higher BMI, fat mass index, and leptin concentrations from the age of 12 yr, whereas the associations show a dip at ages 13-14 yr and become stronger at age 17 yr. The dip is presumably caused by the dominating endocrinological changes at midpuberty.