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.

dx.doi.org/10.1093/hmg/ddv472, hdl.handle.net/1765/87963
Human Molecular Genetics
This work was funded by the European Commission 7th Framework Programme; grant id fp7/201413 - European Network for Genetic and Genomic Epidemiology (ENGAGE), This work was funded by the European Commission 7th Framework Programme; grant id fp7/282957 - Developmental neurotoxicity assessment of mixtures in children (DENAMIC), This work was funded by the European Commission 7th Framework Programme; grant id fp7/279153 - Beta-cell function in juvenile diabetes and obesity (BETA-JUDO), This work was funded by the European Commission 7th Framework Programme; grant id fp7/241592 - European Obesity Consortium studying the Hypothalamus and its Interaction with Peripheral organs. (EUROCHIP)
Department of Pediatrics

Felix, J.F, Bradfield, J.P, Poppelaars-Monnereau, C, van der Valk, R.J.P, Stergiakouli, E, Chesi, A, … Kelly, A. (2016). Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index. Human Molecular Genetics, 25(2), 389–403. doi:10.1093/hmg/ddv472