BMJ open · 2026
Early-life body mass index and adult fat distribution: a life-course Mendelian randomisation study.
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Lai Qiankun, Wang Yanxia, Wang Xiaorong, Ma Guolan, Yang Bingquan, Song Jing, Gao Juan
Аннотация
OBJECTIVES: 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.
DESIGN: Two-sample Mendelian randomisation study using univariable Mendelian randomisation (UVMR) and multivariable Mendelian randomisation (MVMR).
DATA SOURCES: 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.
EXPOSURES: Genetically predicted BMI at birth; 6 weeks; 3, 6 and 8 months; and 1, 1.5, 2, 3, 5, 7 and 8 years.
MAIN OUTCOME MEASURES: Adult abdominal subcutaneous adipose tissue adjusted for BMI (ASATadj), gluteofemoral adipose tissue adjusted for BMI (GFATadj) and visceral adipose tissue adjusted for BMI (VATadj).
RESULTS: 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.
CONCLUSIONS: 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.
DESIGN: Two-sample Mendelian randomisation study using univariable Mendelian randomisation (UVMR) and multivariable Mendelian randomisation (MVMR).
DATA SOURCES: 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.
EXPOSURES: Genetically predicted BMI at birth; 6 weeks; 3, 6 and 8 months; and 1, 1.5, 2, 3, 5, 7 and 8 years.
MAIN OUTCOME MEASURES: Adult abdominal subcutaneous adipose tissue adjusted for BMI (ASATadj), gluteofemoral adipose tissue adjusted for BMI (GFATadj) and visceral adipose tissue adjusted for BMI (VATadj).
RESULTS: 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.
CONCLUSIONS: 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.