ESPE Abstracts

Context: Puberty timing is highly heritable. Recent genome-wide association studies, comparing timing of menarche in girls to timing of voice-break and facial hair in boys, revealed a largely overlapping genetic architecture of female and male pubertal timing. However, it is also known that genetic heterogeneity between sexes exists for some loci.

Objectives: We hypothesized that self-reported relative parental pubertal timing is associated with timing of pubertal milestones in offspring of concordant sex – but that associations may diverge in offspring of discordant sex.

Participants & Methods: Population-based mixed cross-sectional and longitudinal cohort of 1381 healthy children (821 girls and 560 boys; COPENHAGEN Puberty Study; cross-sectional: n=1244, longitudinal: n=137) that underwent blood sampling including measurement of reproductive hormones and clinical examinations including assessment of four/five pubertal milestones in girls/boys, respectively. Their parents answered a questionnaire on their relative (early/average/late) pubertal timing and age at menarche.

Results: We observed significant associations of relative parental pubertal timing with timing of all pubertal milestones in offspring of concordant sex, i.e. fathers/sons (e.g. testicular enlargement ≥4mL: P=0.004, β = 0.34 (SE: 0.10) years per relative category) and mothers/daughters (e.g. thelarche: P<0.001, β = 0.45 (SE: 0.10) years per relative category). Age at menarche in mothers was associated with all pubertal milestones in girls, except axillary hair growth. Concerning pubertal timing in offspring of discordant sex, i.e mother/sons and father/daughter, the results were more heterogeneous. While relative pubertal timing in fathers was significantly associated with timing of pubarche and menarche (P=0.03 and 0.01, respectively) in girls, it was not associated with thelarche or axillary hair growth. Relative pubertal timing in mothers was significantly associated with timing of testicular enlargement, pubarche and voice-break in boys (P=0.002, 0.001 and 0.001, respectively), but not with sweat odor or axillary hair growth. Self-reported age at menarche in mothers was associated with all pubertal milestones in boys, except sweat odor. We further tested hormonal outcomes, i.e. Testosterone above limit of detection (>0.23nmol/L) in boys and Luteinizing Hormone >0.3IU/L in girls, and observed a similar pattern of significant associations in concordant sex and no association in discordant sex.

Conclusion: We demonstrate that self-reported pubertal timing in parents is consistently associated with timing of pubertal milestones in offspring of concordant sex but only inconsistently with milestones in discordant sex pointing to a distinct heterogeneity in the genetic architecture of timing of pubertal milestones between sexes.