Epigenetic association analysis of clinical sub-phenotypes in patients with polycystic ovary syndrome (PCOS)

Vibe Maria Jacobsen, Shuxia Li, Ancong Wang, Dongyi Zhu, Min Liu, Mads Thomassen, Torben A Kruse, Qihua Tan*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Polycystic ovarian syndrome (PCOS) is a complex disorder affecting up to 15-20% of reproductive women. PCOS has recently been investigated using genome-wide association studies revealing important mutations and DNA methylation sites associated with the syndrome. As a clinically highly heterogenous condition, studying the molecular basis of the differential manifestation of PCOS is both meaningful concerning individualized management and important for understanding the biology of PCOS. Using genome-wide DNA methylation data collected from PCOS patients, we performed a powerful region-based analysis to detect differentially methylated regions (DMR) by correlating DNA methylation pattern in a genomic region with the level of each PCOS clinical sub-phenotype. We identified seven significant DMRs on chromosome 19 (12877188-12876846 bp) and chromosome 6 (MHC region) associated with prolactin level, as well as chromosomes 11 and 2 associated with metabolic attributes. Functional annotation linked significant DNA methylation patterns to functional genes (HOOK2, BDNFl, HLA-G, HLA-H, HLA-J, RNF39, etc) of metabolic disorders and immunity or novel associations to serve as targets for validation and replication.
Original languageEnglish
JournalGynecological Endocrinology
Volume35
Issue number8
Pages (from-to)691-694
ISSN0951-3590
DOIs
Publication statusPublished - 3. Aug 2019

Fingerprint

Polycystic Ovary Syndrome
Epigenomics
DNA Methylation
HLA-G Antigens
Chromosomes, Human, Pair 19
Chromosomes, Human, Pair 11
Chromosomes, Human, Pair 6
Chromosomes, Human, Pair 2
Genome-Wide Association Study
Prolactin
Mutation

Keywords

  • DNA methylation; PCOS; clinical heterogeneity; differentially methylated regions
  • PCOS
  • DNA methylation
  • clinical heterogeneity
  • differentially methylated regions

Cite this

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title = "Epigenetic association analysis of clinical sub-phenotypes in patients with polycystic ovary syndrome (PCOS)",
abstract = "Polycystic ovarian syndrome (PCOS) is a complex disorder affecting up to 15-20{\%} of reproductive women. PCOS has recently been investigated using genome-wide association studies revealing important mutations and DNA methylation sites associated with the syndrome. As a clinically highly heterogenous condition, studying the molecular basis of the differential manifestation of PCOS is both meaningful concerning individualized management and important for understanding the biology of PCOS. Using genome-wide DNA methylation data collected from PCOS patients, we performed a powerful region-based analysis to detect differentially methylated regions (DMR) by correlating DNA methylation pattern in a genomic region with the level of each PCOS clinical sub-phenotype. We identified seven significant DMRs on chromosome 19 (12877188-12876846 bp) and chromosome 6 (MHC region) associated with prolactin level, as well as chromosomes 11 and 2 associated with metabolic attributes. Functional annotation linked significant DNA methylation patterns to functional genes (HOOK2, BDNFl, HLA-G, HLA-H, HLA-J, RNF39, etc) of metabolic disorders and immunity or novel associations to serve as targets for validation and replication.",
keywords = "DNA methylation; PCOS; clinical heterogeneity; differentially methylated regions, PCOS, DNA methylation, clinical heterogeneity, differentially methylated regions",
author = "Jacobsen, {Vibe Maria} and Shuxia Li and Ancong Wang and Dongyi Zhu and Min Liu and Mads Thomassen and Kruse, {Torben A} and Qihua Tan",
year = "2019",
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language = "English",
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pages = "691--694",
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Epigenetic association analysis of clinical sub-phenotypes in patients with polycystic ovary syndrome (PCOS). / Jacobsen, Vibe Maria; Li, Shuxia; Wang, Ancong ; Zhu, Dongyi ; Liu, Min ; Thomassen, Mads; Kruse, Torben A; Tan, Qihua.

In: Gynecological Endocrinology, Vol. 35, No. 8, 03.08.2019, p. 691-694.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Epigenetic association analysis of clinical sub-phenotypes in patients with polycystic ovary syndrome (PCOS)

AU - Jacobsen, Vibe Maria

AU - Li, Shuxia

AU - Wang, Ancong

AU - Zhu, Dongyi

AU - Liu, Min

AU - Thomassen, Mads

AU - Kruse, Torben A

AU - Tan, Qihua

PY - 2019/8/3

Y1 - 2019/8/3

N2 - Polycystic ovarian syndrome (PCOS) is a complex disorder affecting up to 15-20% of reproductive women. PCOS has recently been investigated using genome-wide association studies revealing important mutations and DNA methylation sites associated with the syndrome. As a clinically highly heterogenous condition, studying the molecular basis of the differential manifestation of PCOS is both meaningful concerning individualized management and important for understanding the biology of PCOS. Using genome-wide DNA methylation data collected from PCOS patients, we performed a powerful region-based analysis to detect differentially methylated regions (DMR) by correlating DNA methylation pattern in a genomic region with the level of each PCOS clinical sub-phenotype. We identified seven significant DMRs on chromosome 19 (12877188-12876846 bp) and chromosome 6 (MHC region) associated with prolactin level, as well as chromosomes 11 and 2 associated with metabolic attributes. Functional annotation linked significant DNA methylation patterns to functional genes (HOOK2, BDNFl, HLA-G, HLA-H, HLA-J, RNF39, etc) of metabolic disorders and immunity or novel associations to serve as targets for validation and replication.

AB - Polycystic ovarian syndrome (PCOS) is a complex disorder affecting up to 15-20% of reproductive women. PCOS has recently been investigated using genome-wide association studies revealing important mutations and DNA methylation sites associated with the syndrome. As a clinically highly heterogenous condition, studying the molecular basis of the differential manifestation of PCOS is both meaningful concerning individualized management and important for understanding the biology of PCOS. Using genome-wide DNA methylation data collected from PCOS patients, we performed a powerful region-based analysis to detect differentially methylated regions (DMR) by correlating DNA methylation pattern in a genomic region with the level of each PCOS clinical sub-phenotype. We identified seven significant DMRs on chromosome 19 (12877188-12876846 bp) and chromosome 6 (MHC region) associated with prolactin level, as well as chromosomes 11 and 2 associated with metabolic attributes. Functional annotation linked significant DNA methylation patterns to functional genes (HOOK2, BDNFl, HLA-G, HLA-H, HLA-J, RNF39, etc) of metabolic disorders and immunity or novel associations to serve as targets for validation and replication.

KW - DNA methylation; PCOS; clinical heterogeneity; differentially methylated regions

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KW - clinical heterogeneity

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