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Epigenetic heterogeneity in women with polycystic ovary syndrome
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DOI：10.1016/j.mce.2026.112807.png)
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Abstract
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• We performed an epigenome-wide association study (EWAS) on DNA methylation variability to investigate the epigenetic heterogeneity in polycystic ovary syndrome (PCOS) and to explore the molecular basis in PCOS clinical heterogeneity. • We identified 136 DNA methylation sites that are significantly highly variable in PCOS cases (p<1×10−7). • The EWAS results were significantly enriched for biological pathways including non-alcoholic fatty liver disease, polycomb repressive complex, and Hippo signaling pathway, all have been reportedly to involve in PCOS physiopathology. • Based on the identified significant methylation sites, we were able to cluster PCOS cases into two major clusters which correlate with four reproductive hormones i.e. estradiol, progesterone, thyroid stimulating hormone and testosterone with high statistical significance (p=1.50×10−3). • Our results showed that variability analysis of the PCOS DNA methylome can be a valuable approach for exploring the biological basis in PCOS clinical heterogeneity to promote individualized treatment and management.
Keywords:
DNA methylation
polycystic ovary syndrome
epigenetic heterogeneity
reproductive hormones
clinical heterogeneity
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