Genetic trajectories in childhood BMI linked to later cardiometabolic risk

Distinct genetic patterns shaping body mass index (BMI) from infancy to adolescence have been linked to later-life risk of metabolic disease in a recent analysis, highlighting potential windows for early prevention.

Childhood BMI is known to be a strong predictor of adult obesity and cardiometabolic disease, but the extent to which genetic effects vary across development is unclear.

Published in the journal Nature Communications, a longitudinal analysis led by researchers at the University of Queensland and using data from the Avon Longitudinal Study of Parents and Children, based at the University of Bristol, aimed to characterise how genetic influences on BMI change across early life and whether these differ from those affecting adult BMI.

The researchers analysed 6,291 participants with 65,930 repeated BMI measurements collected between the ages of one and 18 years. A random regression model was applied to estimate single-nucleotide polymorphism (SNP)-based heritability, genetic correlations across ages and patterns of variation over time.

Distinct genetic influences across childhood BMI trajectories

Genetic contributions to BMI were evident throughout childhood, with SNP-based heritability ranging from 23% to 30% across ages and 28.4% at 9.5 years. These effects also influenced the rate of change, with the heritability for trajectory slope estimated at 23.8%.

Importantly, genetic correlations between BMI at different ages declined as the age gap increased. For example, correlation between ages one and two years was high (r_g=0.948, standard error [SE] 0.015), but between one and 10 years was not significantly different from zero (r_g =−0.009, SE 0.142).

These findings indicate that the genetic determinants of BMI in infancy differ from those in later childhood and adolescence.

Principal component analysis showed that one dominant genetic axis accounted for approximately 89% of genetic variation, with effects increasing through childhood and plateauing at around 10 years of age.

A second axis, explaining around 9% of the variance, showed opposing effects between early life and adolescence, supporting distinct developmental profiles.

Links to diabetes and cardiovascular risk

Genetic analyses demonstrated associations between BMI trajectories and adult cardiometabolic traits. The rate of change in childhood showed genetic correlations with type 2 diabetes risk (r_g =0.578, SE 0.135), HbA1c (r_g =0.339, 95% CI 0.210–0.468), glucose (r_g =0.282, 95% CI 0.147–0.417) and hypertension (r_g =0.235, 95% CI 0.119–0.351).

The study also identified genetic loci associated with BMI trajectory features, including variants in FTO and ADCY3 that influenced mean BMI and its change over time.

While limitations, including the relatively modest sample size, limited data density at younger ages and restriction to individuals of European ancestry, must be considered, the findings underscore the importance of monitoring BMI patterns in early life, rather than relying on single-time-point measures. This will allow for a better understanding of long-term cardiometabolic risk.

The authors noted that future research should replicate their findings in more diverse populations with denser early-life data and explore causal relationships between childhood BMI trajectories and adult disease.

Reference
Wang G et al. Distinct genetic profiles influence body mass index between infancy and adolescence. Nat Commun 2026;17:1594.