Associations between genetic obesity susceptibility and early postnatal fat and lean mass: an individual participant meta-analysis.
Elks CE., Heude B., de Zegher F., Barton SJ., Clément K., Inskip HM., Koudou Y., Cooper C., Dunger DB., Ibáñez L., Charles MA., Ong KK.
Patterns of body size and body composition associated with genetic obesity susceptibility inform the mechanisms that increase obesity risk.To test associations between genetic obesity susceptibility, represented by a combined obesity risk-allele score, and body size or body composition at birth to age 5 years.A total of 3031 children from 4 birth cohort studies in England, France, and Spain were included in a meta-analysis.A combined obesity risk-allele score was calculated from genotypes at 16 variants identified by genome-wide association studies of adult body mass index (BMI).Outcomes were age- and sex-adjusted SD scores (SDS) for weight, length/height, BMI, fat mass, lean mass, and percentage of body fat at birth as well as at ages 1, 2 to 3, and 4 to 5 years.The obesity risk-allele score was not associated with infant size at birth; at age 1 year it was positively associated with weight (β [SE], 0.020 [0.008] SDS per allele; P = .009) and length (β [SE], 0.020 [0.008] SDS per allele; P = .01), but not with BMI (β [SE], 0.013 [0.008] SDS per allele; P = .11). At age 2 to 3 years these associations were stronger (weight: β [SE], 0.033 [0.008] SDS per allele; P < .001; height: β [SE], 0.025 [0.008] SDS per allele; P < .001) and were also seen for BMI (β [SE], 0.024 [0.008] SDS per allele; P = .003). The obesity risk-allele score was positively associated with both postnatal fat mass (1 year: β [SE], 0.032 [0.017] SDS per allele; P = .05; 2-3 years: β [SE], 0.049 [0.018] SDS per allele; P = .006; and 4-5 years: β [SE], 0.028 [0.011] SDS per allele; P = .009) and postnatal lean mass (1 year: β [SE], 0.038 [0.014] SDS per allele; P = .008; 2-3 years: β [SE], 0.064 [0.017] SDS per allele; P < .001; and 4-5 years: β [SE], 0.047 [0.011] SDS per allele; P < .001), but not with the percentage of body fat (P > .15 at all ages).Genetic obesity susceptibility appears to promote a normally partitioned increase in early postnatal, but not prenatal, growth. These findings suggest that symmetrical rapid growth may identify infants with high life-long susceptibility for obesity.