Abstract
CONTEXT: Voice break, as a landmark of advanced male puberty in genome-wide association studies (GWAS), has revealed that pubertal timing is a highly polygenic trait. Although voice break is easily recorded in large cohorts, it holds quite low precision as a marker of puberty. In contrast, gonadarche and pubarche are early and clinically well-defined measures of puberty onset.
OBJECTIVE: To determine whether a polygenic risk score (PRS) of alleles that confer risk for voice break associates with age at gonadarche (AAG) and age at pubarche (AAP) in Chilean boys.
EXPERIMENTAL DESIGN: Longitudinal study.
SUBJECTS AND METHODS: 401 boys from the Growth and Obesity Chilean Cohort Study (n = 1194; 49.2% boys).
MAIN OUTCOME MEASURES: Biannual clinical pubertal staging including orchidometry. AAG and AAP were estimated by censoring methods. Genotyping was performed using the Multi-Ethnic Global Array (Illumina). Using GWAS summary statistics from the UK-Biobank, 29 significant and independent single nucleotide polymorphisms associated with age at voice break were extracted. Individual PRS were computed as the sum of risk alleles weighted by the effect size.
RESULTS: The PRS was associated with AAG (β=0.01, P = 0.04) and AAP (β=0.185, P = 0.0004). In addition, boys within the 20% highest PRS experienced gonadarche and pubarche 0.55 and 0.67 years later than those in the lowest 20%, respectively (P = 0.013 and P = 0.007).
CONCLUSIONS: Genetic variants identified in large GWAS on age at VB significantly associate with age at testicular growth and pubic hair development, suggesting that these events share a genetic architecture across ethnically distinct populations.
Originalsprog | Engelsk |
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Artikelnummer | dgaa003 |
Tidsskrift | The Journal of clinical endocrinology and metabolism |
Vol/bind | 105 |
Udgave nummer | 3 |
Sider (fra-til) | E349-E357 |
ISSN | 0021-972X |
DOI | |
Status | Udgivet - 1 mar. 2020 |