Objective: Large-scale genome-wide association (GWA) studies have so far identified 16 loci incontrovertibly associated with obesity-related traits in adults. We examined associations of variants in these loci with anthropometric traits in children/adolescents.

Research design and methods: Seventeen variants representing 16 obesity-susceptibility loci were genotyped in 1,252 children (mean±SD age: 9.7±0.4yrs) and 790 adolescents (15.5±0.5yrs) from the European Youth Heart Study (EYHS). We tested for association of individual variants and a genetic predisposition score (GPS-17), calculated by summing the number of effect-alleles, with anthropometric traits. For 13 variants, summary statistics for associations with BMI were meta-analysed with previously reported data (N_total=13,071 children/adolescents).

Results: In EYHS, 15 variants showed associations or trends with anthropometric traits that were directionally consistent with earlier reports in adults. The meta-analysis showed directionally consistent associations with BMI for all 13 variants of which 9 were significant (0.033-0.098SD/allele, P<0.05). The near-TMEM18 variant had the strongest effect (0.098SD/allele, P=8.5·10⁻¹¹). Effect sizes for BMI tended to be more pronounced in children/adolescents than reported earlier in adults for variants in/near SEC16B, TMEM18 and KCTD15, (0.028-0.035SD/allele higher), and less pronounced for rs925946 in BDNF (0.028SD/allele lower). Each additional effect-allele in the GPS-17 was associated with an increase of 0.034SD in BMI (P=3.6·10⁻⁵), 0.039SD in sum of skinfolds (P=1.7·10⁻⁷) and 0.022SD in waist circumference (P=1.7·10⁻⁴), comparable with reported results in adults (0.039SD/allele for BMI, 0.033SD/allele for waist circumference).

Conclusions: Most obesity-susceptibility loci identified by GWA studies in adults are already associated with anthropometric traits in children/adolescents. While the association of some variants may differ with age, the cumulative effect size is similar.