Journal Article

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

Hagen, Casper P, Odroniec, Amadeusz, Juul, Anders, Busch, Alexander Siegfried, Upners, Emmie N, Fischer, Margit Bistrup, Ljubicic, Marie Lindhardt

2024

Overview

Abstract 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-PGSadult were significant associated with mean T-SDSinfancy, mean SHBG-SDSinfancy, and mean LH-SDSinfancy (P = .02, <.001 and .03, with r2 = 0.05, 0.21 and 0.04, respectively). SHBG-PGSadult was significantly associated with mean SHBG-SDSinfancy (P < .001, r2 = 0.18). T-PGSadult explained 5% and 21% of the phenotypic variation in infancy of mean T-SDSinfancy and SHBG-SDSinfancy, 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.

• Publisher: Oxford University Press
• Subject: Adult / Birth Cohort / Blood / Genetic aspects / Globulins / Hormones / Humans / Hypothalamic-pituitary-gonadal axis / Hypothalamus / Infant / Infant, Newborn / Infants / Infants (Newborn) / Life span / Longitudinal Studies / Luteinizing hormone / Luteinizing Hormone - blood / Male / Medical examination / Multifactorial Inheritance / Neonates / Phenotypic variations / Pituitary / Pituitary-gonadal axis / Prospective Studies / Sex Hormone-Binding Globulin - analysis / Sex Hormone-Binding Globulin - metabolism / Sex hormones / Sexual Maturation - physiology / Steroid hormones / Testosterone / Testosterone - blood