Genetic Susceptibility to Obesity and Related Traits in Childhood and Adolescence

Abstract

OBJECTIVE—Large-scale genome-wide association (GWA) studies have thus far identified 16 loci incontrovertibly associ- ated with obesity-related traits in adults. We examined associa- tions of variants in these loci with anthropometric traits in children and adolescents. children and adolescents). RESEARCH DESIGN AND METHODS—Seventeen variants representing 16 obesity susceptibility loci were genotyped in 1,252 children (mean  SD age 9.7  0.4 years) and 790 adolescents (15.5  0.5 years) from the European Youth Heart Study (EYHS). We tested for association of individual variants and a genetic predisposition score (GPS-17), calculated by sum- ming the number of effect alleles, with anthropometric traits. For 13 variants, summary statistics for associations with BMI were meta-analyzed with previously reported data (Ntotal  13,071 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 direc- tionally consistent associations with BMI for all 13 variants, of which 9 were significant (0.033–0.098 SD/allele; P  0.05). The near-TMEM18 variant had the strongest effect (0.098 SD/allele P  8.5  1011 ). Effect sizes for BMI tended to be more pronounced in children and adolescents than reported earlier in adults for variants in or near SEC16B, TMEM18, and KCTD15, (0.028–0.035 SD/allele higher) and less pronounced for rs925946 in BDNF (0.028 SD/allele lower). Each additional effect allele in the GPS-17 was associated with an increase of 0.034 SD in BMI (P  3.6  105 and 0.022 SD in waist circumference (P  1.7  104 ), 0.039 SD, in sum of skinfolds (P  1.7  107 ), which is ), comparable with reported results in adults (0.039 SD/allele for BMI and 0.033 SD/allele for waist circumference). CONCLUSIONS—Most obesity susceptibility loci identified by GWA studies in adults are already associated with anthropomet- ric traits in children/adolescents. Whereas the association of some variants may differ with age, the cumulative effect size is similar. Diabetes