Differential DNA methylation patterns of polycystic ovarian syndrome in whole blood of Chinese women

Shuxia Li, Dongyi Zhu, Hongmei Duan, Anran Ren, Dorte Glintborg, Marianne Andersen, Vibe Skov, Mads Thomassen, Torben Kruse, Qihua Tan*

*Corresponding author for this work

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Abstract

As a universally common endocrinopathy in women of reproductive age, the polycystic ovarian syndrome is characterized by composite clinical phenotypes reflecting the contributions of reproductive impact of ovarian dysfunction and metabolic abnormalities with widely varying symptoms resulting from interference of the genome with the environment through integrative biological mechanisms including epigenetics. We have performed a genome-wide DNA methylation analysis on polycystic ovarian syndrome and identified a substantial number of genomic sites differentially methylated in the whole blood of PCOS patients and healthy controls (52 sites, false discovery rate < 0.05 and corresponding p value < 5.68e-06), highly consistently replicating biological pathways extensively implicated in immunity and immunity-related inflammatory disorders (false discovery rate < 0.05) that were reportedly regulated in the DNA methylome from ovarian tissue under PCOS condition. Most importantly, our genome-wide profiling focusing on PCOS patients revealed a large number of DNA methylation sites and their enriched functional pathways significantly associated with diverse clinical features (levels of prolactin, estradiol, progesterone and menstrual cycle) that could serve as novel molecular basis of the clinical heterogeneity observed in PCOS women.

Original languageEnglish
JournalOncotarget
Volume8
Issue number13
Pages (from-to)20656-20666
ISSN1949-2553
DOIs
Publication statusPublished - 2017

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Polycystic Ovary Syndrome
DNA Methylation
Epigenomics
Prolactin
DNA

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@article{7092df8d94464a759674cf886cd8bffd,
title = "Differential DNA methylation patterns of polycystic ovarian syndrome in whole blood of Chinese women",
abstract = "As a universally common endocrinopathy in women of reproductive age, the polycystic ovarian syndrome is characterized by composite clinical phenotypes reflecting the contributions of reproductive impact of ovarian dysfunction and metabolic abnormalities with widely varying symptoms resulting from interference of the genome with the environment through integrative biological mechanisms including epigenetics. We have performed a genome-wide DNA methylation analysis on polycystic ovarian syndrome and identified a substantial number of genomic sites differentially methylated in the whole blood of PCOS patients and healthy controls (52 sites, false discovery rate < 0.05 and corresponding p value < 5.68e-06), highly consistently replicating biological pathways extensively implicated in immunity and immunity-related inflammatory disorders (false discovery rate < 0.05) that were reportedly regulated in the DNA methylome from ovarian tissue under PCOS condition. Most importantly, our genome-wide profiling focusing on PCOS patients revealed a large number of DNA methylation sites and their enriched functional pathways significantly associated with diverse clinical features (levels of prolactin, estradiol, progesterone and menstrual cycle) that could serve as novel molecular basis of the clinical heterogeneity observed in PCOS women.",
keywords = "DNA methylation, clinical heterogeneity, genome-wide association study, Polycystic ovarian syndrome",
author = "Shuxia Li and Dongyi Zhu and Hongmei Duan and Anran Ren and Dorte Glintborg and Marianne Andersen and Vibe Skov and Mads Thomassen and Torben Kruse and Qihua Tan",
year = "2017",
doi = "10.18632/oncotarget.9327",
language = "English",
volume = "8",
pages = "20656--20666",
journal = "OncoTarget",
issn = "1949-2553",
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Differential DNA methylation patterns of polycystic ovarian syndrome in whole blood of Chinese women. / Li, Shuxia; Zhu, Dongyi; Duan, Hongmei; Ren, Anran; Glintborg, Dorte; Andersen, Marianne; Skov, Vibe; Thomassen, Mads; Kruse, Torben; Tan, Qihua.

In: Oncotarget, Vol. 8, No. 13, 2017, p. 20656-20666.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Differential DNA methylation patterns of polycystic ovarian syndrome in whole blood of Chinese women

AU - Li, Shuxia

AU - Zhu, Dongyi

AU - Duan, Hongmei

AU - Ren, Anran

AU - Glintborg, Dorte

AU - Andersen, Marianne

AU - Skov, Vibe

AU - Thomassen, Mads

AU - Kruse, Torben

AU - Tan, Qihua

PY - 2017

Y1 - 2017

N2 - As a universally common endocrinopathy in women of reproductive age, the polycystic ovarian syndrome is characterized by composite clinical phenotypes reflecting the contributions of reproductive impact of ovarian dysfunction and metabolic abnormalities with widely varying symptoms resulting from interference of the genome with the environment through integrative biological mechanisms including epigenetics. We have performed a genome-wide DNA methylation analysis on polycystic ovarian syndrome and identified a substantial number of genomic sites differentially methylated in the whole blood of PCOS patients and healthy controls (52 sites, false discovery rate < 0.05 and corresponding p value < 5.68e-06), highly consistently replicating biological pathways extensively implicated in immunity and immunity-related inflammatory disorders (false discovery rate < 0.05) that were reportedly regulated in the DNA methylome from ovarian tissue under PCOS condition. Most importantly, our genome-wide profiling focusing on PCOS patients revealed a large number of DNA methylation sites and their enriched functional pathways significantly associated with diverse clinical features (levels of prolactin, estradiol, progesterone and menstrual cycle) that could serve as novel molecular basis of the clinical heterogeneity observed in PCOS women.

AB - As a universally common endocrinopathy in women of reproductive age, the polycystic ovarian syndrome is characterized by composite clinical phenotypes reflecting the contributions of reproductive impact of ovarian dysfunction and metabolic abnormalities with widely varying symptoms resulting from interference of the genome with the environment through integrative biological mechanisms including epigenetics. We have performed a genome-wide DNA methylation analysis on polycystic ovarian syndrome and identified a substantial number of genomic sites differentially methylated in the whole blood of PCOS patients and healthy controls (52 sites, false discovery rate < 0.05 and corresponding p value < 5.68e-06), highly consistently replicating biological pathways extensively implicated in immunity and immunity-related inflammatory disorders (false discovery rate < 0.05) that were reportedly regulated in the DNA methylome from ovarian tissue under PCOS condition. Most importantly, our genome-wide profiling focusing on PCOS patients revealed a large number of DNA methylation sites and their enriched functional pathways significantly associated with diverse clinical features (levels of prolactin, estradiol, progesterone and menstrual cycle) that could serve as novel molecular basis of the clinical heterogeneity observed in PCOS women.

KW - DNA methylation

KW - clinical heterogeneity

KW - genome-wide association study

KW - Polycystic ovarian syndrome

U2 - 10.18632/oncotarget.9327

DO - 10.18632/oncotarget.9327

M3 - Journal article

VL - 8

SP - 20656

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JO - OncoTarget

JF - OncoTarget

SN - 1949-2553

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