A Genome-Wide Association Study Of Childhood Body Fatness

Objective This study aimed to uncover genetic contributors to adiposity in early life.Methods A genome-wide association study of childhood body fatness in 34,401 individuals within the Nurses' Health Studies and the Health Professionals Follow-up Study was conducted. Data were imputed to the 1000 Genomes Phase 3 version 5 reference panel.Results A total of 1,354 single-nucleotide polymorphisms (P < 10(-4)) were selected for replication in a previously published genome-wide association study of childhood BMI. Nineteen significant genome-wide (P < 5 x 10(-8)) regions were observed, fourteen of which were previously associated with childhood obesity and five were novel: BNDF (P = 7.58 x 10(-13)), PRKD1 (P = 1.43 x 10(-10)), 20p13 (P = 2.05 x 10(-10)), FHIT (P = 1.77 x 10(-8)), and LOC101927575 (P = 3.22 x 10(-8)). The BNDF, FHIT, and PRKD1 regions were previously associated with adult BMI. LOC101927575 and 20p13 regions have not previously been associated with adiposity phenotypes. In a transcriptome-wide analysis, associations for POMC at 2p23.3 (P = 3.36 x 10(-6)) and with TMEM18 at 2p25.3 (P = 3.53 x 10(-7)) were observed. Childhood body fatness was genetically correlated with hip (r(g )= 0.42, P = 4.44 x 10(-16)) and waist circumference (r(g )= 0.39, P = 5.56 x 10(-16)), as well as age at menarche (r(g )= -0.37, P = 7.96 x 10(-19)).Conclusions Additional loci that contribute to childhood adiposity were identified, further explicating its genetic architecture.