Genome-wide analysis highlights epigenetic link to age at menarche.

Area of Science:

• Reproductive Endocrinology
• Epigenetics
• Genomics

Background:

• Age at menarche is a critical reproductive milestone linked to cancer and metabolic health.
• While genetic factors are implicated, epigenetic mechanisms regulating pubertal timing are underexplored.

Purpose of the Study:

• To investigate whether genome-wide DNA methylation patterns influence age at menarche.

Main Methods:

• A cross-sectional epigenome-wide association study (EWAS) analyzed DNA methylation in blood from 3,429 adult women.
• The study utilized the Illumina HumanMethylation450 BeadChip and identified differentially methylated regions (DMRs).
• Mendelian randomization was employed to assess causal effects of methylation on age at menarche and gene expression.

Main Results:

• Sixty-three DMRs were identified, with the TRIM61 region showing replicated, consistent effects.
• Mendelian randomization suggested that TRIM61 methylation causally influences age at menarche.
• Functional annotation indicated TRIM61's role in regulating chromatin accessibility and transcriptional processes.

Conclusions:

• Epigenetic regulation, specifically TRIM61 methylation, contributes to pubertal timing.
• Findings provide molecular evidence linking reproductive development, epigenetic mechanisms, and long-term health.
• Results may guide future research on epigenetic biomarkers and therapeutic targets for reproductive and metabolic disorders.