Evolving Genetic Influences on Infant Growth: Linking Polygenic Scores, IGF-I, and Growth in Infancy

CONTEXT: Infancy is a critical period of rapid growth shaped by genetic, hormonal, and nutritional factors. Genetic influence on growth transitions from genetic variants associated with birth size to variants related to adult body size, however, the timing and developmental trajectory of these changes remain to be determined.

OBJECTIVE: To investigate how polygenic scores (PGS) for birth weight, adult BMI, height, and circulating levels of IGF-I relate to anthropometric measurements and IGF-I concentrations in healthy infants.

DESIGN: Longitudinal cohort study: COPENHAGEN Minipuberty Study (2016-2018), with repeated anthropometric and hormonal assessments during the first year of life.

SETTING: Population-based.

PATIENTS OR OTHER PARTICIPANTS: 210 healthy, term, singleton newborns (101 female).

MAIN OUTCOME MEASURES: Age-specific standard deviation scores (SDS) for weight, length/height, and IGF-I serum levels; associations with PGSs and IGF-I levels across infancy.

RESULTS: PGS for birth weight was associated with birth-weight SDS (P < 0.001) but not with weight SDS at ∼1 year (P = .07). In contrast, PGSs for adult BMI and adult height were associated with weight and height SDS at ∼1 year (P = .03 and P < .001, respectively). PGS for adult IGF-I was not associated with IGF-I SDS at 1 month but was significantly associated at 6 and 12 months (P < .001).

CONCLUSION: Genetic influences on growth evolve during infancy. While the influence of genetic variants associated with birth size diminishes after birth, polygenic scores for adult traits and IGF-I regulation become increasingly relevant-already during early infancy-highlighting a dynamic transition in the genetic architecture underlying infant growth.