A Genome-Wide Association Study of Childhood Body Fatness.

Abstract

This study aimed to uncover genetic contributors to adiposity in early life. 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. 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 × 10^-8 ) regions were observed, fourteen of which were previously associated with childhood obesity and five were novel: BNDF (P = 7.58 × 10^-13 ), PRKD1 (P = 1.43 × 10^-10 ), 20p13 (P = 2.05 × 10^-10 ), FHIT (P = 1.77 × 10^-8 ), and LOC101927575 (P = 3.22 × 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 × 10^-6 ) and with TMEM18 at 2p25.3 (P = 3.53 × 10^-7 ) were observed. Childhood body fatness was genetically correlated with hip (r_g = 0.42, P = 4.44 × 10^-16 ) and waist circumference (r_g = 0.39, P = 5.56 × 10^-16 ), as well as age at menarche (r_g = -0.37, P = 7.96 × 10^-19 ). Additional loci that contribute to childhood adiposity were identified, further explicating its genetic architecture.