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 x 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/m(2), in Mapuche children compared with Europeans.

Automated summary

In this study, a cross-ethnic study was conducted on 904 admixed children, and regulatory variants of the immune gene HLA-DQB3 were found to be strongly associated with BMI in children aged 1.5-2.5 years old. A variant in the sex-determining gene DMRT1 was associated with the age at adiposity rebound in girls. BMI was significantly higher in Mapuche children than in Europeans between the ages of 5.5 and 16.5. Finally, compared with European children, Mapuche children had a significantly lower age at adiposity rebound by 1.94 years and a significantly higher BMI at adiposity rebound by 1.2 kg/m(2).