María C Lardone 1 , Alexander S Busch 2 , José L Santos 3 , Patricio Miranda 3 , Susana Eyheramendy 4 , Ana Pereira 5 , Anders Juul 2 , Kristian Almstrup 2 , Verónica Mericq 1 Show Affiliations »
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. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Entities: Disease
Species
Keywords:
GWAS; gonadarche; male puberty; polygenic risk score; pubarche
Mesh： See more »
Substances： See more »
Year: 2020
PMID： 31915828 DOI： 10.1210/clinem/dgaa003
Source DB: PubMed Journal: J Clin Endocrinol Metab ISSN： 0021-972X Impact factor: 5.958