GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI

Early childhood growth patterns are associated with adult health, yet the geneticfactors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studieswith modeling of longitudinal growth traits to study the geneticsof infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinantsof these traits overlap with those of adult health. We found a robust overlap between the geneticsof child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct geneticmakeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different geneticfactors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.