Distinct genetic profiles influence body mass index between infancy and adolescence

Abstract

Body mass index (BMI) changes throughout life with age-varying genetic contributions. We aimed to investigate the genetic contribution to BMI across early life using repeated measures from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Random regression modelling was used to estimate the genetic covariance matrix (Kg) of BMI trajectories from ages one to 18 years with 65,930 repeated BMI measurements from 6,291 genotyped ALSPAC participants. The Kg matrix was used to estimate SNP-based heritability [Formula] at yearly intervals from 1-18 years and genetic correlations across early life. We also performed an eigenvalue decomposition of Kg to identify age-varying genetic patterns of BMI. Finally, we investigated the impact of a polygenic score derived from adult BMI on the estimated genetic components across early life. The [Formula] was relatively constant across early life, between 23-30%. The genetic contribution to BMI in early childhood is different to that in later childhood, indicated by the diminishing strength of genetic correlation across different ages. The eigenvalue decomposition revealed that the primary axis of variation (explaining 89% of the genetic variance in Kg) increases with age from zero and reaches a plateau in adolescence, while the second eigenfunction (explaining around 9% of Kg) represents factors with opposing effects on BMI between early and later ages. Adjusting for the adult BMI polygenic score attenuated the [Formula] from late childhood; for example, [Formula] is 29.8% (SE=6.5%) at 18 years of age and attenuates to 14.5% (SE=6.3%) after adjusting for the adult BMI polygenic score. Although common genetic variation explains around 23-30% of BMI variability across early life, our findings indicate that there is a different genetic profile operating during infancy compared to later childhood and adolescence.