How is "Puberty Timing" encoded by the genome?
The timing of experiencing major puberty milestones can vary significantly within populations and are usually due to a broad range of environmental and genetic factors. However, several studies have reported that earlier puberty timing is associated with higher risks for a range of diseases later in life, such as heart disease and Type 2 diabetes.
To date, scientific understanding of the genetic influence on puberty timing is mainly based on studies conducted on women. As the age of the first period, menstrual bleeding is a well-recalled and widely measured marker of female sexual development. A recent large-scale genome-wide association study (GWAS) for AAM in up to 370,000 women identified 389 independent signals, accounting for approximately one-quarter of the estimated heritability for the trait. In contrast, genetic studies of puberty timing in men are much fewer and smaller in scale due largely to the lack of data on male pubertal milestones.
In this context, researchers performed a multi-trait genome-wide association study (GWAS) for male puberty timing with an effective sample size of 205,354 men. This is the extended study of their previously reported GWAS for age at voice breaking based on data from 23andMe by combining additional data from the UK Biobank study. They combined GWAS summary statistics from five correlated traits using multi-trait analysis of GWAS (MTAG) methodology. The five traits evaluated in this study include age at voice breaking (as measured in the 23andMe study), relatively early and late voice breaking (UK Biobank), and relatively early and late facial hair (UK Biobank). In this four-fold increased sample size, the number of genomic loci identified that have male-specific effects on puberty timing was increased from 5 previously identified to 29 currently. They identified 7,897 variants associated with male puberty timing at the genome-wide statistical significance threshold, comprising 76 independent signals. One of these independent variants is rs913588 in the Lysine-specific demethylase 4C (KDM4C) gene, which has been reported to be related with the age of the first period in women. One of the other significant SNPs is rs7896371 in the Adenosine Deaminase RNA Specific B2 (ADARB2) gene. The G allele of rs913588 and the T allele of rs7896371 showed associations with relatively late-onset puberty in this study population.
Apart from other puberty and growth-related traits, additional analysis of male puberty timing and other complex traits and diseases showed that early puberty is associated with ‘overall health rating,’ followed by several social traits, including educational attainment, fluid intelligence score, and ages at first/last birth. Conversely, later male puberty timing showed negative genetic correlations with heart diseases, including Type 2 diabetes and hypertension, and risky health behaviors, including alcohol intake frequency and smoking. In general, early genetically predicted puberty timing in men was correlated with adverse health outcomes. Read more about the study here:
https://pubmed.ncbi.nlm.nih.gov/32210231/
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