Early-life body mass index and adult fat distribution: a life-course Mendelian randomisation study.

Abstract

Body mass index (BMI) changes dynamically during early life, but whether BMI at specific developmental stages is associated with adult regional fat distribution remains uncertain. We evaluated age-specific associations of genetically predicted childhood BMI with adult MRI-derived BMI-adjusted fat depots and examined whether these associations were independent of adolescent BMI. Two-sample Mendelian randomisation study using univariable Mendelian randomisation (UVMR) and multivariable Mendelian randomisation (MVMR). Publicly available genome-wide association study summary statistics for BMI at 12 early-life time points from birth to 8 years, adolescent BMI from the Early Growth Genetics Consortium and adult MRI-derived adipose depot traits from UK Biobank. Genetically predicted BMI at birth; 6 weeks; 3, 6 and 8 months; and 1, 1.5, 2, 3, 5, 7 and 8 years. Adult abdominal subcutaneous adipose tissue adjusted for BMI (ASATadj), gluteofemoral adipose tissue adjusted for BMI (GFATadj) and visceral adipose tissue adjusted for BMI (VATadj). UVMR showed age-specific heterogeneity. Higher genetically predicted BMI at 1.5 and 2 years was associated with higher adult ASATadj, whereas GFATadj showed no consistent pattern. VATadj showed the clearest signal: higher genetically predicted BMI at 5 and 7 years was associated with lower adult VATadj, with a nominal inverse association at 8 years. After conditioning on adolescent BMI, most early-life associations attenuated, but inverse associations of BMI at 5 and 7 years with VATadj remained nominally significant. Genetically predicted early-life BMI showed stage-specific associations with adult BMI-adjusted fat distribution. Most associations appeared to reflect continuity of body size across the life course, whereas later childhood may warrant further investigation as a possible developmental period related to adult visceral fat partitioning.