RESUMO
CONTEXT: A close link between body mass index (BMI) and female pubertal onset is well established. However, observations in boys remain inconclusive. OBJECTIVE: We aim to determine whether BMI as well as total and central adiposity in prepubertal Chilean boys is associated with pubertal timing. METHODS: We performed a longitudinal study in which 494 boys from the Growth and Obesity Chilean Cohort Study were followed starting from birth and throughout puberty, including 5 prepubertal visits. The main outcome measures included anthropometric data and semi-annual clinical pubertal staging. The association between BMI, obesity (BMI standard deviation score [SDS] ≥ 2) and central adiposity (waist circumference ≥ 90th centile) with precocious puberty and age at gonadarche was analyzed using survival- and logistic regression models. RESULTS: BMI, prevalence of total obesity, and central obesity increased throughout childhood. Among the study population, 45 boys entered puberty before the age of 9 years (9.1%). Obesity at 4 to 7 years and childhood mean BMI SDS were significantly associated with precocious gonadarche. Mean age at testicular enlargement (≥4 mL), was 11.0 years (95% CI, 10.9-11.1) and was inversely associated with BMI SDS, waist circumference, and percentage fat mass in almost all prepubertal visits. Age at testicular enlargement in normal weight, overweight, and obese boys was 11.2 (11.0-11.3), 10.9 (10.6-11.1) and 10.7 (10.4-11.1) years, respectively. CONCLUSION: Our observation supports the association of BMI SDS and obesity with pubertal timing and precocious gonadarche in boys, respectively. Early intervention controlling the obesity epidemic could be useful in decreasing detrimental impact on later health.
Assuntos
Obesidade Abdominal/epidemiologia , Obesidade Infantil/epidemiologia , Puberdade Precoce/epidemiologia , Puberdade/fisiologia , Adiposidade/fisiologia , Fatores Etários , Idade de Início , Criança , Pré-Escolar , Chile/epidemiologia , Estudos de Coortes , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Obesidade Abdominal/complicações , Obesidade Infantil/complicações , Puberdade Precoce/etiologia , Fatores de RiscoRESUMO
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 (nâ =â 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 (ß=0.01, Pâ =â 0.04) and AAP (ß=0.185, Pâ =â 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 (Pâ =â 0.013 and Pâ =â 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.
Assuntos
Biomarcadores , Herança Multifatorial/genética , Puberdade/genética , Voz/genética , Adolescente , Fatores Etários , Biomarcadores/análise , Criança , Pré-Escolar , Chile , Estudos de Coortes , Feminino , Estudo de Associação Genômica Ampla , Humanos , Estudos Longitudinais , Masculino , Puberdade/fisiologia , Projetos de Pesquisa , Fatores Sexuais , Voz/fisiologiaRESUMO
Context: Although genetic factors play a pivotal role in male pubertal timing, genome-wide association studies have identified only a few loci. Genetic variation of follicle-stimulating hormone (FSH) action affects adult reproductive parameters and female pubertal timing. Objective: To investigate whether genetic variation affecting FSH action is associated with onset of puberty in boys. Design: Cross-sectional and longitudinal study of two cohorts of healthy boys. Setting: This was a population-based study. Patients or Other Participants: Danish (n = 1130) and Chilean (n = 424) boys were followed through puberty and genotyped for FSHB c.-211G>T, FSHR c.-29A>G, and FSHR c.2039G>A. Main Outcome Measures: Clinical pubertal staging including orchidometry, anthropometry, and serum gonadotropin levels. Results: Although the cohorts differed markedly (e.g., body composition and genotype frequencies), genetic variation affecting FSH production (FSHB c.-211G>T) was associated with age at pubertal onset, as assessed by testicular enlargement, in both cohorts. The effect appeared further modified by coexistence of genetic variation affecting FSH sensitivity (FSHR c.-29G>A): After correcting for body mass index (BMI), boys with a ligand-receptor variant combination resulting in weak FSH action (i.e., FSHB c.-211GT/TT and FSHR c.-29AA) entered puberty 0.64 years [95% confidence interval (CI), 0.12 to 1.17 years; Denmark] and 0.94 years (95% CI, 0.00 to 1.88 years; Chile) later than boys with the most effective FSH action. Effects explained 1.7% (Denmark) and 1.5% (Chile) of the variance. In addition, BMI z score was negatively associated with pubertal timing (ß = -0.35 years in both cohorts), explaining 17.2% (Denmark) and 7.2% (Chile) of the variance. Conclusion: In two ethnically distinct populations, we independently identified an association of two genetic loci with male pubertal timing.