Predictors of global methylation levels in blood DNA of healthy subjects: A combined analysis

Zhong Zheng Zhu; Lifang Hou; Valentina Bollati; Letizia Tarantini; Barbara Marinelli; Laura Cantone; Allen S. Yang; Pantel Vokonas; Jolanta Lissowska; Silvia Fustinoni; Angela C. Pesatori; Matteo Bonzini; Pietro Apostoli; Giovanni Costa; Pier Alberto Bertazzi; Wong Ho Chow; Joel Schwartz; Andrea Baccarelli

doi:10.1093/ije/dyq154

Predictors of global methylation levels in blood DNA of healthy subjects: A combined analysis

Zhong Zheng Zhu, Lifang Hou, Valentina Bollati, Letizia Tarantini, Barbara Marinelli, Laura Cantone, Allen S. Yang, Pantel Vokonas, Jolanta Lissowska, Silvia Fustinoni, Angela C. Pesatori, Matteo Bonzini, Pietro Apostoli, Giovanni Costa, Pier Alberto Bertazzi, Wong Ho Chow, Joel Schwartz, Andrea Baccarelli^*

^*Corresponding author for this work

Preventive Medicine

Research output: Contribution to journal › Article › peer-review

175 Scopus citations

Abstract

Background: Estimates of global DNA methylation from repetitive DNA elements, such as Alu and LINE-1, have been increasingly used in epidemiological investigations because of their relative low-cost, high-throughput and quantitative results. Nevertheless, determinants of these methylation measures in healthy individuals are still largely unknown. The aim of this study was to examine whether age, gender, smoking habits, alcohol drinking and body mass index (BMI) are associated with Alu or LINE-1 methylation levels in blood leucocyte DNA of healthy individuals. Methods: Individual data from five studies including a total of 1465 healthy subjects were combined. DNA methylation was quantified by PCR-pyrosequencing. Results: Age [β = -0.011% of 5-methyl-cytosine (%5mC)/year, 95% confidence interval (CI) -0.020 to -0.001%5mC/year] and alcohol drinking (β = -0.214, 95% CI -0.415 to -0.013) were inversely associated with Alu methylation. Compared with females, males had lower Alu methylation (β = -0.385, 95% CI -0.665 to -0.104) and higher LINE-1 methylation (β = 0.796, 95% CI 0.261 to 1.330). No associations were found with smoking or BMI. Percent neutrophils and lymphocytes in blood counts exhibited a positive (β = 0.036, 95% CI 0.010 to 0.061) and negative (β = -0.038, 95% CI -0.065 to -0.012) association with LINE-1 methylation, respectively. Conclusions: Global methylation measures in blood DNA vary in relation with certain host and lifestyle characteristics, including age, gender, alcohol drinking and white blood cell counts. These findings need to be considered in designing epidemiological investigations aimed at identifying associations between DNA methylation and health outcomes. Published by Oxford University Press on behalf of the International Epidemiological Association

Original language	English (US)
Article number	dyq154
Pages (from-to)	126-139
Number of pages	14
Journal	International journal of epidemiology
Volume	41
Issue number	1
DOIs	https://doi.org/10.1093/ije/dyq154
State	Published - Feb 2012

Funding

Study 1: National Institute of Environmental Health Sciences [ES015172-01] and Environmental Protection Agency [R83241601, R827353]. The VA Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC). Study 2: Intramural Research Program (Division of Cancer Epidemiology and Genetics, NCI) of the National Institutes of Health, Diane Belfer Program for Human Microbial Diversity and the National Institutes of Health [R01GM63270]. Study 3: Italian Association for Cancer Research (AIRC) (2008–10) [6016]. Study 4: Cariplo Foundation [2007-5469] and Italian Ministry of Scientific Research (MIUR) [PRIN-20072S2HT8]. Study 5: Milan University intramural funding.

Keywords

Blood
DNA methylation
Epigenetics
Meta-analysis
Repetitive elements

ASJC Scopus subject areas

Epidemiology

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10.1093/ije/dyq154

Cite this

Zhu, Z. Z., Hou, L., Bollati, V., Tarantini, L., Marinelli, B., Cantone, L., Yang, A. S., Vokonas, P., Lissowska, J., Fustinoni, S., Pesatori, A. C., Bonzini, M., Apostoli, P., Costa, G., Bertazzi, P. A., Chow, W. H., Schwartz, J., & Baccarelli, A. (2012). Predictors of global methylation levels in blood DNA of healthy subjects: A combined analysis. International journal of epidemiology, 41(1), 126-139. Article dyq154. https://doi.org/10.1093/ije/dyq154

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title = "Predictors of global methylation levels in blood DNA of healthy subjects: A combined analysis",

abstract = "Background: Estimates of global DNA methylation from repetitive DNA elements, such as Alu and LINE-1, have been increasingly used in epidemiological investigations because of their relative low-cost, high-throughput and quantitative results. Nevertheless, determinants of these methylation measures in healthy individuals are still largely unknown. The aim of this study was to examine whether age, gender, smoking habits, alcohol drinking and body mass index (BMI) are associated with Alu or LINE-1 methylation levels in blood leucocyte DNA of healthy individuals. Methods: Individual data from five studies including a total of 1465 healthy subjects were combined. DNA methylation was quantified by PCR-pyrosequencing. Results: Age [β = -0.011% of 5-methyl-cytosine (%5mC)/year, 95% confidence interval (CI) -0.020 to -0.001%5mC/year] and alcohol drinking (β = -0.214, 95% CI -0.415 to -0.013) were inversely associated with Alu methylation. Compared with females, males had lower Alu methylation (β = -0.385, 95% CI -0.665 to -0.104) and higher LINE-1 methylation (β = 0.796, 95% CI 0.261 to 1.330). No associations were found with smoking or BMI. Percent neutrophils and lymphocytes in blood counts exhibited a positive (β = 0.036, 95% CI 0.010 to 0.061) and negative (β = -0.038, 95% CI -0.065 to -0.012) association with LINE-1 methylation, respectively. Conclusions: Global methylation measures in blood DNA vary in relation with certain host and lifestyle characteristics, including age, gender, alcohol drinking and white blood cell counts. These findings need to be considered in designing epidemiological investigations aimed at identifying associations between DNA methylation and health outcomes. Published by Oxford University Press on behalf of the International Epidemiological Association",

keywords = "Blood, DNA methylation, Epigenetics, Meta-analysis, Repetitive elements",

author = "Zhu, {Zhong Zheng} and Lifang Hou and Valentina Bollati and Letizia Tarantini and Barbara Marinelli and Laura Cantone and Yang, {Allen S.} and Pantel Vokonas and Jolanta Lissowska and Silvia Fustinoni and Pesatori, {Angela C.} and Matteo Bonzini and Pietro Apostoli and Giovanni Costa and Bertazzi, {Pier Alberto} and Chow, {Wong Ho} and Joel Schwartz and Andrea Baccarelli",

note = "Funding Information: Study 1: National Institute of Environmental Health Sciences [ES015172-01] and Environmental Protection Agency [R83241601, R827353]. The VA Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC). Study 2: Intramural Research Program (Division of Cancer Epidemiology and Genetics, NCI) of the National Institutes of Health, Diane Belfer Program for Human Microbial Diversity and the National Institutes of Health [R01GM63270]. Study 3: Italian Association for Cancer Research (AIRC) (2008–10) [6016]. Study 4: Cariplo Foundation [2007-5469] and Italian Ministry of Scientific Research (MIUR) [PRIN-20072S2HT8]. Study 5: Milan University intramural funding.",

year = "2012",

month = feb,

doi = "10.1093/ije/dyq154",

language = "English (US)",

volume = "41",

pages = "126--139",

journal = "International journal of epidemiology",

issn = "0300-5771",

publisher = "Oxford University Press",

number = "1",

}

Zhu, ZZ, Hou, L, Bollati, V, Tarantini, L, Marinelli, B, Cantone, L, Yang, AS, Vokonas, P, Lissowska, J, Fustinoni, S, Pesatori, AC, Bonzini, M, Apostoli, P, Costa, G, Bertazzi, PA, Chow, WH, Schwartz, J & Baccarelli, A 2012, 'Predictors of global methylation levels in blood DNA of healthy subjects: A combined analysis', International journal of epidemiology, vol. 41, no. 1, dyq154, pp. 126-139. https://doi.org/10.1093/ije/dyq154

TY - JOUR

T1 - Predictors of global methylation levels in blood DNA of healthy subjects

T2 - A combined analysis

AU - Zhu, Zhong Zheng

AU - Hou, Lifang

AU - Bollati, Valentina

AU - Tarantini, Letizia

AU - Marinelli, Barbara

AU - Cantone, Laura

AU - Yang, Allen S.

AU - Vokonas, Pantel

AU - Lissowska, Jolanta

AU - Fustinoni, Silvia

AU - Pesatori, Angela C.

AU - Bonzini, Matteo

AU - Apostoli, Pietro

AU - Costa, Giovanni

AU - Bertazzi, Pier Alberto

AU - Chow, Wong Ho

AU - Schwartz, Joel

AU - Baccarelli, Andrea

N1 - Funding Information: Study 1: National Institute of Environmental Health Sciences [ES015172-01] and Environmental Protection Agency [R83241601, R827353]. The VA Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC). Study 2: Intramural Research Program (Division of Cancer Epidemiology and Genetics, NCI) of the National Institutes of Health, Diane Belfer Program for Human Microbial Diversity and the National Institutes of Health [R01GM63270]. Study 3: Italian Association for Cancer Research (AIRC) (2008–10) [6016]. Study 4: Cariplo Foundation [2007-5469] and Italian Ministry of Scientific Research (MIUR) [PRIN-20072S2HT8]. Study 5: Milan University intramural funding.

PY - 2012/2

Y1 - 2012/2

N2 - Background: Estimates of global DNA methylation from repetitive DNA elements, such as Alu and LINE-1, have been increasingly used in epidemiological investigations because of their relative low-cost, high-throughput and quantitative results. Nevertheless, determinants of these methylation measures in healthy individuals are still largely unknown. The aim of this study was to examine whether age, gender, smoking habits, alcohol drinking and body mass index (BMI) are associated with Alu or LINE-1 methylation levels in blood leucocyte DNA of healthy individuals. Methods: Individual data from five studies including a total of 1465 healthy subjects were combined. DNA methylation was quantified by PCR-pyrosequencing. Results: Age [β = -0.011% of 5-methyl-cytosine (%5mC)/year, 95% confidence interval (CI) -0.020 to -0.001%5mC/year] and alcohol drinking (β = -0.214, 95% CI -0.415 to -0.013) were inversely associated with Alu methylation. Compared with females, males had lower Alu methylation (β = -0.385, 95% CI -0.665 to -0.104) and higher LINE-1 methylation (β = 0.796, 95% CI 0.261 to 1.330). No associations were found with smoking or BMI. Percent neutrophils and lymphocytes in blood counts exhibited a positive (β = 0.036, 95% CI 0.010 to 0.061) and negative (β = -0.038, 95% CI -0.065 to -0.012) association with LINE-1 methylation, respectively. Conclusions: Global methylation measures in blood DNA vary in relation with certain host and lifestyle characteristics, including age, gender, alcohol drinking and white blood cell counts. These findings need to be considered in designing epidemiological investigations aimed at identifying associations between DNA methylation and health outcomes. Published by Oxford University Press on behalf of the International Epidemiological Association

AB - Background: Estimates of global DNA methylation from repetitive DNA elements, such as Alu and LINE-1, have been increasingly used in epidemiological investigations because of their relative low-cost, high-throughput and quantitative results. Nevertheless, determinants of these methylation measures in healthy individuals are still largely unknown. The aim of this study was to examine whether age, gender, smoking habits, alcohol drinking and body mass index (BMI) are associated with Alu or LINE-1 methylation levels in blood leucocyte DNA of healthy individuals. Methods: Individual data from five studies including a total of 1465 healthy subjects were combined. DNA methylation was quantified by PCR-pyrosequencing. Results: Age [β = -0.011% of 5-methyl-cytosine (%5mC)/year, 95% confidence interval (CI) -0.020 to -0.001%5mC/year] and alcohol drinking (β = -0.214, 95% CI -0.415 to -0.013) were inversely associated with Alu methylation. Compared with females, males had lower Alu methylation (β = -0.385, 95% CI -0.665 to -0.104) and higher LINE-1 methylation (β = 0.796, 95% CI 0.261 to 1.330). No associations were found with smoking or BMI. Percent neutrophils and lymphocytes in blood counts exhibited a positive (β = 0.036, 95% CI 0.010 to 0.061) and negative (β = -0.038, 95% CI -0.065 to -0.012) association with LINE-1 methylation, respectively. Conclusions: Global methylation measures in blood DNA vary in relation with certain host and lifestyle characteristics, including age, gender, alcohol drinking and white blood cell counts. These findings need to be considered in designing epidemiological investigations aimed at identifying associations between DNA methylation and health outcomes. Published by Oxford University Press on behalf of the International Epidemiological Association

KW - Blood

KW - DNA methylation

KW - Epigenetics

KW - Meta-analysis

KW - Repetitive elements

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U2 - 10.1093/ije/dyq154

DO - 10.1093/ije/dyq154

M3 - Article

C2 - 20846947

AN - SCOPUS:84858680246

SN - 0300-5771

VL - 41

SP - 126

EP - 139

JO - International journal of epidemiology

JF - International journal of epidemiology

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Predictors of global methylation levels in blood DNA of healthy subjects: A combined analysis

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