Polygenic Scores for Adult Testosterone and SHBG Levels Are Associated With Reproductive Hormone Levels in Male Infants.

Context The hypothalamic-pituitary-gonadal axis's transient activity in infancy, i.e, minipuberty, is considered crucial for male reproductive function. Historically, minipuberty has been considered a passive response triggered by the withdrawal of placental steroids at birth. However, given its potential link to adult reproductive function, we hypothesize that minipuberty is a partially genetically regulated process, suggesting a link between the genetic architecture of reproductive hormone concentrations across lifespan. Objective To investigate the association of UK Biobank Study-based polygenic scores (PGS) of adult total testosterone (T) and sex hormone-binding globulin (SHBG) concentrations with trajectories of reproductive hormones concentrations in male infants. Design Prospective, longitudinal birth cohort (The COPENHAGEN Minipuberty Study, 2016-2018, ClinTrial: NCT02784184). Individual PGSs in male infants derived from published literature were calculated for total T and SHBG. The associations with mean SD scores (SDS) of reproductive hormone concentrations in infancy were tested. Setting Population-based. Patients or other participants Healthy, male, term, singleton newborns were followed with repeated clinical examinations including blood sampling during a 1-year follow-up (n = 109). Main outcome measures Circulating reproductive hormone concentrations. Results T-PGS_adult were significant associated with mean T-SDS_infancy, mean SHBG-SDS_infancy, and mean LH-SDS_infancy (P =.02, <.001 and.03, with r² = 0.05, 0.21 and 0.04, respectively). SHBG-PGS_adult was significantly associated with mean SHBG-SDS_infancy (P <.001, r² = 0.18). T-PGS_adult explained 5% and 21% of the phenotypic variation in infancy of mean T-SDS_infancy and SHBG-SDS_infancy, respectively. Conclusion Our findings suggest that the genetic architecture underlying total T and SHBG in adults also associates with hormone concentrations and their trajectories during infancy. [ABSTRACT FROM AUTHOR]