Adult adiposity susceptibility loci, early growth and general and abdominal fatness in childhood: the Generation R Study.

Abstract

Genome-wide association studies in adults have identified genetic loci associated with adiposity measures. Little is known about the effects of these loci on growth and body fat distribution from early childhood onwards. In a population-based prospective cohort study among 4144 children, we examined the associations of weighted risk scores combining 29 known genetic markers of adult body mass index (BMI) and 14 known genetic markers of adult waist-hip ratio (WHR) with peak weight velocity, peak height velocity, age at adiposity peak and BMI at adiposity peak in early infancy and additionally with BMI, total fat mass, android/gynoid fat ratio and preperitoneal fat area at the median age of 6.0 years (95% range 5.7, 7.8). A higher adult BMI genetic risk score was associated with a higher age at adiposity peak in infancy and a higher BMI, total fat mass, android/gynoid fat ratio and preperitoneal fat area in childhood (P=0.05, 1.5 × 10(-24), 3.6 × 10(-18), 4.0 × 10(-11) and 1.3 × 10(-5), respectively), with the strongest association for childhood BMI with a 0.04 higher s.d. score BMI (95% confidence interval 0.03, 0.05) per additional risk allele. A higher adult WHR genetic risk score was not associated with infant growth measures or childhood BMI and total fat mass, but was associated with childhood android/gynoid fat ratio and preperitoneal fat area (P<0.05). Genetic variants associated with BMI and WHR in adults influence growth patterns and general and abdominal fat development from early childhood onwards.