Methylome analysis and epigenetic changes associated with menarcheal age

Reproductive factors have been linked to both breast cancer and DNA methylation, suggesting methylation as an important mechanism by which reproductive factors impact on disease risk. However, few studies have investigated the link between reproductive factors and DNA methylation in humans. Genome-w...

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Published in:PloS one 2013-11, Vol.8 (11), p.e79391-e79391
Main Authors: Demetriou, Christiana A, Chen, Jia, Polidoro, Silvia, van Veldhoven, Karin, Cuenin, Cyrille, Campanella, Gianluca, Brennan, Kevin, Clavel-Chapelon, Françoise, Dossus, Laure, Kvaskoff, Marina, Drogan, Dagmar, Boeing, Heiner, Kaaks, Rudolf, Risch, Angela, Trichopoulos, Dimitrios, Lagiou, Pagona, Masala, Giovanna, Sieri, Sabina, Tumino, Rosario, Panico, Salvatore, Quirós, J Ramón, Sánchez Perez, María-José, Amiano, Pilar, Huerta Castaño, José María, Ardanaz, Eva, Onland-Moret, Charlotte, Peeters, Petra, Khaw, Kay-Tee, Wareham, Nick, Key, Timothy J, Travis, Ruth C, Romieu, Isabelle, Gallo, Valentina, Gunter, Marc, Herceg, Zdenko, Kyriacou, Kyriacos, Riboli, Elio, Flanagan, James M, Vineis, Paolo
Format: Article
Language:English
Subjects:
Adult
Age
Aged
Alcohol use
Analysis
Body measurements
Breast cancer
Cancer genetics
Cell cycle
Chronic illnesses
Clinical medicine
CpG islands
CpG Islands - genetics
Deoxyribonucleic acid
DNA
DNA methylation
DNA Methylation - genetics
Epidemiology
Epigenesis, Genetic - genetics
Epigenetic inheritance
Epigenetics
Female
Genetics
Genomes
Genomics
Health care
Health risks
Health sciences
Hormones
Humans
Loci
Lymphocytes
Medical research
Menarche
Menarche - genetics
Menarche - physiology
Methylation
Microscopy
Middle Aged
Mutation
Nutrition
Peripheral blood
Population
Preventive medicine
Primary care
Prospective Studies
Public health
Regression analysis
Risk analysis
Risk factors
Women's health
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container_end_page e79391
container_issue 11
container_start_page e79391
container_title PloS one
container_volume 8
creator Demetriou, Christiana A
Chen, Jia
Polidoro, Silvia
van Veldhoven, Karin
Cuenin, Cyrille
Campanella, Gianluca
Brennan, Kevin
Clavel-Chapelon, Françoise
Dossus, Laure
Kvaskoff, Marina
Drogan, Dagmar
Boeing, Heiner
Kaaks, Rudolf
Risch, Angela
Trichopoulos, Dimitrios
Lagiou, Pagona
Masala, Giovanna
Sieri, Sabina
Tumino, Rosario
Panico, Salvatore
Quirós, J Ramón
Sánchez Perez, María-José
Amiano, Pilar
Huerta Castaño, José María
Ardanaz, Eva
Onland-Moret, Charlotte
Peeters, Petra
Khaw, Kay-Tee
Wareham, Nick
Key, Timothy J
Travis, Ruth C
Romieu, Isabelle
Gallo, Valentina
Gunter, Marc
Herceg, Zdenko
Kyriacou, Kyriacos
Riboli, Elio
Flanagan, James M
Vineis, Paolo
description Reproductive factors have been linked to both breast cancer and DNA methylation, suggesting methylation as an important mechanism by which reproductive factors impact on disease risk. However, few studies have investigated the link between reproductive factors and DNA methylation in humans. Genome-wide methylation in peripheral blood lymphocytes of 376 healthy women from the prospective EPIC study was investigated using LUminometric Methylation Assay (LUMA). Also, methylation of 458877 CpG sites was additionally investigated in an independent group of 332 participants of the EPIC-Italy sub-cohort, using the Infinium HumanMethylation 450 BeadChip. Multivariate logistic regression and linear models were used to investigate the association between reproductive risk factors and genome wide and CpG-specific DNA methylation, respectively. Menarcheal age was inversely associated with global DNA methylation as measured with LUMA. For each yearly increase in age at menarche, the risk of having genome wide methylation below median level was increased by 32% (OR:1.32, 95%CI:1.14-1.53). When age at menarche was treated as a categorical variable, there was an inverse dose-response relationship with LUMA methylation levels (OR(12-14 vs. ≤11 yrs):1.78, 95%CI:1.01-3.17 and OR(≥15 vs. ≤11 yrs):4.59, 95%CI:2.04-10.33; P for trend
doi_str_mv 10.1371/journal.pone.0079391
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However, few studies have investigated the link between reproductive factors and DNA methylation in humans. Genome-wide methylation in peripheral blood lymphocytes of 376 healthy women from the prospective EPIC study was investigated using LUminometric Methylation Assay (LUMA). Also, methylation of 458877 CpG sites was additionally investigated in an independent group of 332 participants of the EPIC-Italy sub-cohort, using the Infinium HumanMethylation 450 BeadChip. Multivariate logistic regression and linear models were used to investigate the association between reproductive risk factors and genome wide and CpG-specific DNA methylation, respectively. Menarcheal age was inversely associated with global DNA methylation as measured with LUMA. For each yearly increase in age at menarche, the risk of having genome wide methylation below median level was increased by 32% (OR:1.32, 95%CI:1.14-1.53). When age at menarche was treated as a categorical variable, there was an inverse dose-response relationship with LUMA methylation levels (OR(12-14 vs. ≤11 yrs):1.78, 95%CI:1.01-3.17 and OR(≥15 vs. ≤11 yrs):4.59, 95%CI:2.04-10.33; P for trend&lt;0.0001). However, average levels of global methylation as measured by the Illumina technology were not significantly associated with menarcheal age. In locus by locus comparative analyses, only one CpG site had significantly different methylation depending on the menarcheal age category examined, but this finding was not replicated by pyrosequencing in an independent data set. This study suggests a link between age at menarche and genome wide DNA methylation, and the difference in results between the two arrays suggests that repetitive element methylation has a role in the association. Epigenetic changes may be modulated by menarcheal age, or the association may be a mirror of other important changes in early life that have a detectable effect on both methylation levels and menarcheal age.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0079391</identifier><identifier>PMID: 24278132</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Age ; Aged ; Alcohol use ; Analysis ; Body measurements ; Breast cancer ; Cancer genetics ; Cell cycle ; Chronic illnesses ; Clinical medicine ; CpG islands ; CpG Islands - genetics ; Deoxyribonucleic acid ; DNA ; DNA methylation ; DNA Methylation - genetics ; Epidemiology ; Epigenesis, Genetic - genetics ; Epigenetic inheritance ; Epigenetics ; Female ; Genetics ; Genomes ; Genomics ; Health care ; Health risks ; Health sciences ; Hormones ; Humans ; Loci ; Lymphocytes ; Medical research ; Menarche ; Menarche - genetics ; Menarche - physiology ; Methylation ; Microscopy ; Middle Aged ; Mutation ; Nutrition ; Peripheral blood ; Population ; Preventive medicine ; Primary care ; Prospective Studies ; Public health ; Regression analysis ; Risk analysis ; Risk factors ; Women's health</subject><ispartof>PloS one, 2013-11, Vol.8 (11), p.e79391-e79391</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Demetriou et al. 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However, few studies have investigated the link between reproductive factors and DNA methylation in humans. Genome-wide methylation in peripheral blood lymphocytes of 376 healthy women from the prospective EPIC study was investigated using LUminometric Methylation Assay (LUMA). Also, methylation of 458877 CpG sites was additionally investigated in an independent group of 332 participants of the EPIC-Italy sub-cohort, using the Infinium HumanMethylation 450 BeadChip. Multivariate logistic regression and linear models were used to investigate the association between reproductive risk factors and genome wide and CpG-specific DNA methylation, respectively. Menarcheal age was inversely associated with global DNA methylation as measured with LUMA. For each yearly increase in age at menarche, the risk of having genome wide methylation below median level was increased by 32% (OR:1.32, 95%CI:1.14-1.53). When age at menarche was treated as a categorical variable, there was an inverse dose-response relationship with LUMA methylation levels (OR(12-14 vs. ≤11 yrs):1.78, 95%CI:1.01-3.17 and OR(≥15 vs. ≤11 yrs):4.59, 95%CI:2.04-10.33; P for trend&lt;0.0001). However, average levels of global methylation as measured by the Illumina technology were not significantly associated with menarcheal age. In locus by locus comparative analyses, only one CpG site had significantly different methylation depending on the menarcheal age category examined, but this finding was not replicated by pyrosequencing in an independent data set. This study suggests a link between age at menarche and genome wide DNA methylation, and the difference in results between the two arrays suggests that repetitive element methylation has a role in the association. Epigenetic changes may be modulated by menarcheal age, or the association may be a mirror of other important changes in early life that have a detectable effect on both methylation levels and menarcheal age.</description><subject>Adult</subject><subject>Age</subject><subject>Aged</subject><subject>Alcohol use</subject><subject>Analysis</subject><subject>Body measurements</subject><subject>Breast cancer</subject><subject>Cancer genetics</subject><subject>Cell cycle</subject><subject>Chronic illnesses</subject><subject>Clinical medicine</subject><subject>CpG islands</subject><subject>CpG Islands - genetics</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>DNA Methylation - genetics</subject><subject>Epidemiology</subject><subject>Epigenesis, Genetic - genetics</subject><subject>Epigenetic inheritance</subject><subject>Epigenetics</subject><subject>Female</subject><subject>Genetics</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Health care</subject><subject>Health risks</subject><subject>Health sciences</subject><subject>Hormones</subject><subject>Humans</subject><subject>Loci</subject><subject>Lymphocytes</subject><subject>Medical research</subject><subject>Menarche</subject><subject>Menarche - genetics</subject><subject>Menarche - physiology</subject><subject>Methylation</subject><subject>Microscopy</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Nutrition</subject><subject>Peripheral blood</subject><subject>Population</subject><subject>Preventive medicine</subject><subject>Primary care</subject><subject>Prospective Studies</subject><subject>Public health</subject><subject>Regression analysis</subject><subject>Risk analysis</subject><subject>Risk factors</subject><subject>Women's 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analysis and epigenetic changes associated with menarcheal age</title><author>Demetriou, Christiana A ; Chen, Jia ; Polidoro, Silvia ; van Veldhoven, Karin ; Cuenin, Cyrille ; Campanella, Gianluca ; Brennan, Kevin ; Clavel-Chapelon, Françoise ; Dossus, Laure ; Kvaskoff, Marina ; Drogan, Dagmar ; Boeing, Heiner ; Kaaks, Rudolf ; Risch, Angela ; Trichopoulos, Dimitrios ; Lagiou, Pagona ; Masala, Giovanna ; Sieri, Sabina ; Tumino, Rosario ; Panico, Salvatore ; Quirós, J Ramón ; Sánchez Perez, María-José ; Amiano, Pilar ; Huerta Castaño, José María ; Ardanaz, Eva ; Onland-Moret, Charlotte ; Peeters, Petra ; Khaw, Kay-Tee ; Wareham, Nick ; Key, Timothy J ; Travis, Ruth C ; Romieu, Isabelle ; Gallo, Valentina ; Gunter, Marc ; Herceg, Zdenko ; Kyriacou, Kyriacos ; Riboli, Elio ; Flanagan, James M ; Vineis, Paolo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c585t-d40a697ea68fcb54cd1317e9ee918cf912682a018abb3fc35bb95f19b381aeeb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Age</topic><topic>Aged</topic><topic>Alcohol use</topic><topic>Analysis</topic><topic>Body measurements</topic><topic>Breast cancer</topic><topic>Cancer genetics</topic><topic>Cell cycle</topic><topic>Chronic illnesses</topic><topic>Clinical medicine</topic><topic>CpG islands</topic><topic>CpG Islands - genetics</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>DNA Methylation - genetics</topic><topic>Epidemiology</topic><topic>Epigenesis, Genetic - genetics</topic><topic>Epigenetic inheritance</topic><topic>Epigenetics</topic><topic>Female</topic><topic>Genetics</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Health care</topic><topic>Health risks</topic><topic>Health sciences</topic><topic>Hormones</topic><topic>Humans</topic><topic>Loci</topic><topic>Lymphocytes</topic><topic>Medical research</topic><topic>Menarche</topic><topic>Menarche - genetics</topic><topic>Menarche - physiology</topic><topic>Methylation</topic><topic>Microscopy</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Nutrition</topic><topic>Peripheral blood</topic><topic>Population</topic><topic>Preventive medicine</topic><topic>Primary care</topic><topic>Prospective Studies</topic><topic>Public health</topic><topic>Regression analysis</topic><topic>Risk analysis</topic><topic>Risk factors</topic><topic>Women's health</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Demetriou, Christiana A</creatorcontrib><creatorcontrib>Chen, Jia</creatorcontrib><creatorcontrib>Polidoro, Silvia</creatorcontrib><creatorcontrib>van Veldhoven, Karin</creatorcontrib><creatorcontrib>Cuenin, Cyrille</creatorcontrib><creatorcontrib>Campanella, Gianluca</creatorcontrib><creatorcontrib>Brennan, Kevin</creatorcontrib><creatorcontrib>Clavel-Chapelon, Françoise</creatorcontrib><creatorcontrib>Dossus, Laure</creatorcontrib><creatorcontrib>Kvaskoff, Marina</creatorcontrib><creatorcontrib>Drogan, Dagmar</creatorcontrib><creatorcontrib>Boeing, Heiner</creatorcontrib><creatorcontrib>Kaaks, Rudolf</creatorcontrib><creatorcontrib>Risch, Angela</creatorcontrib><creatorcontrib>Trichopoulos, Dimitrios</creatorcontrib><creatorcontrib>Lagiou, Pagona</creatorcontrib><creatorcontrib>Masala, Giovanna</creatorcontrib><creatorcontrib>Sieri, Sabina</creatorcontrib><creatorcontrib>Tumino, Rosario</creatorcontrib><creatorcontrib>Panico, Salvatore</creatorcontrib><creatorcontrib>Quirós, J Ramón</creatorcontrib><creatorcontrib>Sánchez Perez, María-José</creatorcontrib><creatorcontrib>Amiano, Pilar</creatorcontrib><creatorcontrib>Huerta Castaño, José María</creatorcontrib><creatorcontrib>Ardanaz, Eva</creatorcontrib><creatorcontrib>Onland-Moret, Charlotte</creatorcontrib><creatorcontrib>Peeters, Petra</creatorcontrib><creatorcontrib>Khaw, Kay-Tee</creatorcontrib><creatorcontrib>Wareham, Nick</creatorcontrib><creatorcontrib>Key, Timothy J</creatorcontrib><creatorcontrib>Travis, Ruth C</creatorcontrib><creatorcontrib>Romieu, Isabelle</creatorcontrib><creatorcontrib>Gallo, Valentina</creatorcontrib><creatorcontrib>Gunter, Marc</creatorcontrib><creatorcontrib>Herceg, Zdenko</creatorcontrib><creatorcontrib>Kyriacou, Kyriacos</creatorcontrib><creatorcontrib>Riboli, Elio</creatorcontrib><creatorcontrib>Flanagan, James M</creatorcontrib><creatorcontrib>Vineis, Paolo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal 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Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest Health &amp; Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health &amp; Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied &amp; Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Demetriou, Christiana A</au><au>Chen, Jia</au><au>Polidoro, Silvia</au><au>van Veldhoven, Karin</au><au>Cuenin, Cyrille</au><au>Campanella, Gianluca</au><au>Brennan, Kevin</au><au>Clavel-Chapelon, Françoise</au><au>Dossus, Laure</au><au>Kvaskoff, Marina</au><au>Drogan, Dagmar</au><au>Boeing, Heiner</au><au>Kaaks, Rudolf</au><au>Risch, Angela</au><au>Trichopoulos, Dimitrios</au><au>Lagiou, Pagona</au><au>Masala, Giovanna</au><au>Sieri, Sabina</au><au>Tumino, Rosario</au><au>Panico, Salvatore</au><au>Quirós, J Ramón</au><au>Sánchez Perez, María-José</au><au>Amiano, Pilar</au><au>Huerta Castaño, José María</au><au>Ardanaz, Eva</au><au>Onland-Moret, Charlotte</au><au>Peeters, Petra</au><au>Khaw, Kay-Tee</au><au>Wareham, Nick</au><au>Key, Timothy J</au><au>Travis, Ruth C</au><au>Romieu, Isabelle</au><au>Gallo, Valentina</au><au>Gunter, Marc</au><au>Herceg, Zdenko</au><au>Kyriacou, Kyriacos</au><au>Riboli, Elio</au><au>Flanagan, James M</au><au>Vineis, Paolo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Methylome analysis and epigenetic changes associated with menarcheal age</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-11-20</date><risdate>2013</risdate><volume>8</volume><issue>11</issue><spage>e79391</spage><epage>e79391</epage><pages>e79391-e79391</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Reproductive factors have been linked to both breast cancer and DNA methylation, suggesting methylation as an important mechanism by which reproductive factors impact on disease risk. However, few studies have investigated the link between reproductive factors and DNA methylation in humans. Genome-wide methylation in peripheral blood lymphocytes of 376 healthy women from the prospective EPIC study was investigated using LUminometric Methylation Assay (LUMA). Also, methylation of 458877 CpG sites was additionally investigated in an independent group of 332 participants of the EPIC-Italy sub-cohort, using the Infinium HumanMethylation 450 BeadChip. Multivariate logistic regression and linear models were used to investigate the association between reproductive risk factors and genome wide and CpG-specific DNA methylation, respectively. Menarcheal age was inversely associated with global DNA methylation as measured with LUMA. For each yearly increase in age at menarche, the risk of having genome wide methylation below median level was increased by 32% (OR:1.32, 95%CI:1.14-1.53). When age at menarche was treated as a categorical variable, there was an inverse dose-response relationship with LUMA methylation levels (OR(12-14 vs. ≤11 yrs):1.78, 95%CI:1.01-3.17 and OR(≥15 vs. ≤11 yrs):4.59, 95%CI:2.04-10.33; P for trend&lt;0.0001). However, average levels of global methylation as measured by the Illumina technology were not significantly associated with menarcheal age. In locus by locus comparative analyses, only one CpG site had significantly different methylation depending on the menarcheal age category examined, but this finding was not replicated by pyrosequencing in an independent data set. This study suggests a link between age at menarche and genome wide DNA methylation, and the difference in results between the two arrays suggests that repetitive element methylation has a role in the association. Epigenetic changes may be modulated by menarcheal age, or the association may be a mirror of other important changes in early life that have a detectable effect on both methylation levels and menarcheal age.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24278132</pmid><doi>10.1371/journal.pone.0079391</doi><oa>free_for_read</oa></addata></record>
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subjects Adult
Age
Aged
Alcohol use
Analysis
Body measurements
Breast cancer
Cancer genetics
Cell cycle
Chronic illnesses
Clinical medicine
CpG islands
CpG Islands - genetics
Deoxyribonucleic acid
DNA
DNA methylation
DNA Methylation - genetics
Epidemiology
Epigenesis, Genetic - genetics
Epigenetic inheritance
Epigenetics
Female
Genetics
Genomes
Genomics
Health care
Health risks
Health sciences
Hormones
Humans
Loci
Lymphocytes
Medical research
Menarche
Menarche - genetics
Menarche - physiology
Methylation
Microscopy
Middle Aged
Mutation
Nutrition
Peripheral blood
Population
Preventive medicine
Primary care
Prospective Studies
Public health
Regression analysis
Risk analysis
Risk factors
Women's health
title Methylome analysis and epigenetic changes associated with menarcheal age
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