New insights from GWAS on BMI-related growth traits in a longitudinal cohort of admixed children with Native American and European ancestry

Body-mass index (BMI) is a hallmark of adiposity. In contrast with adulthood, the genetic architecture of BMI during childhood is poorly understood. The few genome-wide association studies (GWAS) on children have been performed almost exclusively in Europeans and at single ages. We performed cross-sectional and longitudinal GWAS for BMI-related traits on 904 admixed children with mostly Mapuche Native American and European ancestries. We found regulatory variants of the immune gene HLA-DQB3 strongly associated with BMI at 1.5-2.5 years old. A variant in the sex-determining gene DMRT1 was associated with the age at adiposity rebound (Age-AR) in girls (P=9.8×10-9 ). BMI was significantly higher in Mapuche than in Europeans between 5.5 and 16.5 years old. Finally, Age-AR was significantly lower (P=0.004 ) by 1.94 years and BMI at AR was significantly higher (P=0.04 ) by 1.2 kg/ m2 , in Mapuche children compared with Europeans.