Associations with FTO (fat mass and obesity associated) gene variants and BMI have been reported in western adult populations. To widen the ethnic and age coverage of the FTO studies, we investigated the effects of FTO gene variants on being overweight and related phenotypes in Korean children and adult with a consideration of lifestyle factors. We genotyped 711 children for 2 FTO SNPs (rs9939973 and rs9939609), analyzed lifestyle factors, and investigated the potential involvement of FTO variants in being overweight comparing with 8842 adults in the KSNP database. With a strong association between FTO gene variants and BMI levels, we further identified an association between rs9939973 or rs9939609 and being overweight both children (P=0.025, OR=1.47, 95% CI=1.05-2.06; P=0.023, OR=1.53, 95% CI=1.06-2.22) and adults (P=0.018, OR=1.10, 95% CI=1.02-1.19; P=0.001, OR=1.16, 95% CI=1.06-1.27). Significant association was observed between rs9939609 and dietary fat intake in children (P=0.008) but not in adults. In low physical activity subgroup of children, rs9939609 A allele carriers had a higher BMI than TT carriers (P=0.0147). A significant interaction effect of rs9939609 on BMI across 3 levels of adult physical activity was found. FTO variant rs9939609 is an overweight susceptibility gene in Koreans. By low physical activity, A allele greatly influenced greater BMI. 2010 Elsevier B.V. All rights reserved.