A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10⁻⁸) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10⁻¹⁰) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.

Importance Obesity in adolescence has reached epidemic proportions around the world, with the prevalence of severe obesity increasing at least 4-fold over the last 35 years. Most youths with obesity carry their excess adiposity into adulthood, which places them at increased risk for developing obesity-driven complications, such as type 2 diabetes and cardiovascular disease, and negatively affects social and emotional health. Given that adolescence is a unique transition period marked by significant physiologic and developmental changes, obesity-related complications can also negatively affect adolescent growth and developmental trajectories. Observations Provision of evidence-based treatment options that are tailored and appropriate for the adolescent population is paramount, yet complex. The multifactorial etiology of obesity along with the significant changes that occur during the adolescent period increasingly complicate the treatment approach for adolescent obesity. Treatment practices discussed in this review include an overview of evidence supporting currently available behavioral, pharmacologic, surgical, and device interventions for obesity. However, it is important to note that these practices have not been effective at reducing adolescent obesity at the population level. Conclusions and Relevance Because adolescent obesity requires lifelong treatment, effectively addressing this disease will require significant resources, scientific rigor, and the provision of access to quality care similar to other chronic health conditions. Effective and less invasive therapies, effective adjuncts, and comprehensive centers that offer specialized treatment are critical. This considerable need for increased attention to obesity care calls for dedicated resources in both education and research for treatment of obesity in youths.