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

Busch AS; Ljubicic ML; Upners EN; Fischer MB; Odroniec A; Hagen CP; Juul A

Abstract

CONTEXT - OBJECTIVE - DESIGN - SETTING - PATIENTS OR OTHER PARTICIPANTS - MAIN OUTCOME MEASURES - RESULTS - CONCLUSIONS; The Hypothalamic-Pituitary-Gonadal (HPG) 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.; 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.; 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 testosterone and SHBG. The associations with mean Standard Deviation Scores (SDS) of reproductive hormone concentrations in infancy were tested.; Population-based.; Healthy, male, term, singleton newborns were followed with repeated clinical examinations including blood sampling during a one-year follow-up (n=109).; Circulating reproductive hormone concentrations.; T-PGSadult were significant associated with mean T-SDSinfancy, mean SHBG-SDSinfancy and mean LH-SDSinfancy (p=0.02, <0.001 and 0.03, with r2=0.05, 0.21 and 0.04, respectively). SHBG-PGSadult was significantly associated with mean SHBG-SDSinfancy (p<0.001, r2=0.18). T-PGSadult explained 5% and 21% of the phenotypic variation in infancy of mean T-SDSinfancy and SHBG-SDSinfancy, respectively.; Our findings suggest that the genetic architecture underlying total testosterone and SHBG in adults also associates with hormone concentrations and their trajectories during infancy.