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Global endometrial DNA methylation analysis reveals insights into mQTL regulation and associated endometriosis disease risk and endometrial function
Endometriosis is a leading cause of pain and infertility affecting millions of women globally. Herein, we characterize variation in DNA methylation (DNAm) and its association with menstrual cycle phase, endometriosis, and genetic variants through analysis of genotype data and methylation in endometr...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10432557/ https://www.ncbi.nlm.nih.gov/pubmed/37587191 http://dx.doi.org/10.1038/s42003-023-05070-z |
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author | Mortlock, Sally Houshdaran, Sahar Kosti, Idit Rahmioglu, Nilufer Nezhat, Camran Vitonis, Allison F. Andrews, Shan V. Grosjean, Parker Paranjpe, Manish Horne, Andrew W. Jacoby, Alison Lager, Jeannette Opoku-Anane, Jessica Vo, Kim Chi Manvelyan, Evelina Sen, Sushmita Ghukasyan, Zhanna Collins, Frances Santamaria, Xavier Saunders, Philippa Kober, Kord McRae, Allan F. Terry, Kathryn L. Vallvé-Juanico, Júlia Becker, Christian Rogers, Peter A. W. Irwin, Juan C. Zondervan, Krina Montgomery, Grant W. Missmer, Stacey Sirota, Marina Giudice, Linda |
author_facet | Mortlock, Sally Houshdaran, Sahar Kosti, Idit Rahmioglu, Nilufer Nezhat, Camran Vitonis, Allison F. Andrews, Shan V. Grosjean, Parker Paranjpe, Manish Horne, Andrew W. Jacoby, Alison Lager, Jeannette Opoku-Anane, Jessica Vo, Kim Chi Manvelyan, Evelina Sen, Sushmita Ghukasyan, Zhanna Collins, Frances Santamaria, Xavier Saunders, Philippa Kober, Kord McRae, Allan F. Terry, Kathryn L. Vallvé-Juanico, Júlia Becker, Christian Rogers, Peter A. W. Irwin, Juan C. Zondervan, Krina Montgomery, Grant W. Missmer, Stacey Sirota, Marina Giudice, Linda |
author_sort | Mortlock, Sally |
collection | PubMed |
description | Endometriosis is a leading cause of pain and infertility affecting millions of women globally. Herein, we characterize variation in DNA methylation (DNAm) and its association with menstrual cycle phase, endometriosis, and genetic variants through analysis of genotype data and methylation in endometrial samples from 984 deeply-phenotyped participants. We estimate that 15.4% of the variation in endometriosis is captured by DNAm and identify significant differences in DNAm profiles associated with stage III/IV endometriosis, endometriosis sub-phenotypes and menstrual cycle phase, including opening of the window for embryo implantation. Menstrual cycle phase was a major source of DNAm variation suggesting cellular and hormonally-driven changes across the cycle can regulate genes and pathways responsible for endometrial physiology and function. DNAm quantitative trait locus (mQTL) analysis identified 118,185 independent cis-mQTLs including 51 associated with risk of endometriosis, highlighting candidate genes contributing to disease risk. Our work provides functional evidence for epigenetic targets contributing to endometriosis risk and pathogenesis. Data generated serve as a valuable resource for understanding tissue-specific effects of methylation on endometrial biology in health and disease. |
format | Online Article Text |
id | pubmed-10432557 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-104325572023-08-18 Global endometrial DNA methylation analysis reveals insights into mQTL regulation and associated endometriosis disease risk and endometrial function Mortlock, Sally Houshdaran, Sahar Kosti, Idit Rahmioglu, Nilufer Nezhat, Camran Vitonis, Allison F. Andrews, Shan V. Grosjean, Parker Paranjpe, Manish Horne, Andrew W. Jacoby, Alison Lager, Jeannette Opoku-Anane, Jessica Vo, Kim Chi Manvelyan, Evelina Sen, Sushmita Ghukasyan, Zhanna Collins, Frances Santamaria, Xavier Saunders, Philippa Kober, Kord McRae, Allan F. Terry, Kathryn L. Vallvé-Juanico, Júlia Becker, Christian Rogers, Peter A. W. Irwin, Juan C. Zondervan, Krina Montgomery, Grant W. Missmer, Stacey Sirota, Marina Giudice, Linda Commun Biol Article Endometriosis is a leading cause of pain and infertility affecting millions of women globally. Herein, we characterize variation in DNA methylation (DNAm) and its association with menstrual cycle phase, endometriosis, and genetic variants through analysis of genotype data and methylation in endometrial samples from 984 deeply-phenotyped participants. We estimate that 15.4% of the variation in endometriosis is captured by DNAm and identify significant differences in DNAm profiles associated with stage III/IV endometriosis, endometriosis sub-phenotypes and menstrual cycle phase, including opening of the window for embryo implantation. Menstrual cycle phase was a major source of DNAm variation suggesting cellular and hormonally-driven changes across the cycle can regulate genes and pathways responsible for endometrial physiology and function. DNAm quantitative trait locus (mQTL) analysis identified 118,185 independent cis-mQTLs including 51 associated with risk of endometriosis, highlighting candidate genes contributing to disease risk. Our work provides functional evidence for epigenetic targets contributing to endometriosis risk and pathogenesis. Data generated serve as a valuable resource for understanding tissue-specific effects of methylation on endometrial biology in health and disease. Nature Publishing Group UK 2023-08-16 /pmc/articles/PMC10432557/ /pubmed/37587191 http://dx.doi.org/10.1038/s42003-023-05070-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Mortlock, Sally Houshdaran, Sahar Kosti, Idit Rahmioglu, Nilufer Nezhat, Camran Vitonis, Allison F. Andrews, Shan V. Grosjean, Parker Paranjpe, Manish Horne, Andrew W. Jacoby, Alison Lager, Jeannette Opoku-Anane, Jessica Vo, Kim Chi Manvelyan, Evelina Sen, Sushmita Ghukasyan, Zhanna Collins, Frances Santamaria, Xavier Saunders, Philippa Kober, Kord McRae, Allan F. Terry, Kathryn L. Vallvé-Juanico, Júlia Becker, Christian Rogers, Peter A. W. Irwin, Juan C. Zondervan, Krina Montgomery, Grant W. Missmer, Stacey Sirota, Marina Giudice, Linda Global endometrial DNA methylation analysis reveals insights into mQTL regulation and associated endometriosis disease risk and endometrial function |
title | Global endometrial DNA methylation analysis reveals insights into mQTL regulation and associated endometriosis disease risk and endometrial function |
title_full | Global endometrial DNA methylation analysis reveals insights into mQTL regulation and associated endometriosis disease risk and endometrial function |
title_fullStr | Global endometrial DNA methylation analysis reveals insights into mQTL regulation and associated endometriosis disease risk and endometrial function |
title_full_unstemmed | Global endometrial DNA methylation analysis reveals insights into mQTL regulation and associated endometriosis disease risk and endometrial function |
title_short | Global endometrial DNA methylation analysis reveals insights into mQTL regulation and associated endometriosis disease risk and endometrial function |
title_sort | global endometrial dna methylation analysis reveals insights into mqtl regulation and associated endometriosis disease risk and endometrial function |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10432557/ https://www.ncbi.nlm.nih.gov/pubmed/37587191 http://dx.doi.org/10.1038/s42003-023-05070-z |
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