Associations between genetic variants associated with body mass index and trajectories of body fatness across the life course: a longitudinal analysis

Background: The genetic associations with trajectories of body fatness over the life course remain unknown. Methods: We used a group-based modelling approach to identify trajectories of body fatness from age 5 years up to 65 for 7277 women from the Nurses' Health Study and 4645 men from the Health Professionals Follow-up Study. We created a genetic risk score (GRS) based on 97 variants associated with adulthood body mass index (BMI) and estimated its association with trajectories using logistic regression. Results: We identified four distinct trajectories: lean-medium, medium-medium, leanheavy and medium-heavy. The GRS increased across the four groups in that order (P<0.001); 47% of women and 45% of men in the first decile of the GRS were in the lean-medium group, and these proportions reduced to 26% and 28%, respectively, for the highest decile. The corresponding proportions in the medium-heavy group were 8% and 5%, increasing to 21% and 14%, respectively. For women, compared with the odds of being in the lean-medium group, a 10-allele increment in the GRS was associated with a 40% [95% confidence interval (CI), 27-54%], 43% (30-58%), and 115% (91-143%) increase in the odds of being in the medium-medium, lean-heavy and medium-heavy groups, respectively. For men, the corresponding increases in the odds were 26% (12-42%), 27% (13-43%), and 81% (53-115%), respectively. Conclusions: Individuals with genetic variants for adulthood BMI were more likely to maintain a heavy body shape and gain weight throughout life. These findings support a persistent effect of genetic variants on body fatness across the lifespan.