Association of a Body Mass Index Genetic Risk Score with Growth throughout Childhood and Adolescence

Background: While the number of established genetic variants associated with adult body mass index (BMI) is growing, the relationships between these variants and growth during childhood are yet to be fully characterised. We examined the association between validated adult BMI associated single nucleotide polymorphisms (SNPs) and growth trajectories across childhood. We investigated the timing of onset of the genetic effect and whether it was sex specific. Methods: Children from the ALSPAC and Raine birth cohorts were used for analysis (n=9,328). Genotype data from 32 adult BMI associated SNPs were investigated individually and as an allelic score. Linear mixed effects models with smoothing splines were used for longitudinal modelling of the growth parameters and measures of adiposity peak and rebound were derived. Results: The allelic score was associated with BMI growth throughout childhood, explaining 0.58% of the total variance in BMI in females and 0.44% in males. The allelic score was associated with higher BMI at the adiposity peak (females = 0.0163 kg/m 2 per allele, males = 0.0123 kg/m 2 per allele) and earlier age (-0.0362 years per allele in males and females) and higher BMI (0.0332 kg/m 2 per allele in females and 0.0364 kg/m 2 per allele in males) at the adiposity rebound. No gene:sex interactions were detected for BMI growth. Conclusions: This study suggests that known adult genetic determinants of BMI have observable effects on growth from early childhood, and is consistent with the hypothesis that genetic determinants of adult susceptibility to obesity act from early childhood and develop over the life course.