Smoking-related DNA methylation is associated with DNA methylation phenotypic age acceleration: The veterans affairs normative aging study

Yang Yang, Xu Gao, Allan C. Just, Elena Colicino, Cuicui Wang, Brent A. Coull, Lifang Hou, Yinan Zheng, Pantel Vokonas, Joel Schwartz, Andrea A. Baccarelli*

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

DNA methylation may play a critical role in aging and age-related diseases. DNA methylation phenotypic age (DNAmPhenoAge) is a new aging biomarker and predictor of chronic disease risk. While smoking is a strong risk factor for chronic diseases and influences methylation, its influence on DNAmPhenoAge is unknown. We investigated associations of self-reported and epigenetic smoking indicators with DNAmPhenoAge acceleration in a longitudinal aging study in eastern Massachusetts. DNA methylation was measured in whole blood samples from multiple visits for 692 male participants in the Veterans Affairs Normative Aging Study during 1999–2013. Acceleration was defined using residuals from linear regression of the DNAmPhenoAge on the chronological age. Cumulative smoking (pack-years) was significantly associated with DNAmPhenoAge acceleration, whereas self-reported smoking status was not. We observed significant validated associations between smoking-related loci and DNAmPhenoAge acceleration for 52 CpG sites, where 18 were hypomethylated and 34 were hypermethylated, mapped to 16 genes. The AHRR gene had the most loci (N = 8) among the 16 genes. We generated a smoking aging index based on these 52 loci, which showed positive significant associations with DNAmPhenoAge acceleration. These epigenetic biomarkers may help to predict age-related risks driven by smoking.

Original languageEnglish (US)
Article number2356
JournalInternational journal of environmental research and public health
Volume16
Issue number13
DOIs
StatePublished - Jul 1 2019

Fingerprint

Veterans
DNA Methylation
Smoking
Epigenomics
Chronic Disease
Biomarkers
Genes
Methylation
Longitudinal Studies
Linear Models

Keywords

  • Aging acceleration
  • Aging biomarker
  • DNA methylation phenotypic age
  • Smoking-related DNA methylation

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

Cite this

Yang, Yang ; Gao, Xu ; Just, Allan C. ; Colicino, Elena ; Wang, Cuicui ; Coull, Brent A. ; Hou, Lifang ; Zheng, Yinan ; Vokonas, Pantel ; Schwartz, Joel ; Baccarelli, Andrea A. / Smoking-related DNA methylation is associated with DNA methylation phenotypic age acceleration : The veterans affairs normative aging study. In: International journal of environmental research and public health. 2019 ; Vol. 16, No. 13.
@article{aa8e0b2f0db2473bb4b84308786b4f6d,
title = "Smoking-related DNA methylation is associated with DNA methylation phenotypic age acceleration: The veterans affairs normative aging study",
abstract = "DNA methylation may play a critical role in aging and age-related diseases. DNA methylation phenotypic age (DNAmPhenoAge) is a new aging biomarker and predictor of chronic disease risk. While smoking is a strong risk factor for chronic diseases and influences methylation, its influence on DNAmPhenoAge is unknown. We investigated associations of self-reported and epigenetic smoking indicators with DNAmPhenoAge acceleration in a longitudinal aging study in eastern Massachusetts. DNA methylation was measured in whole blood samples from multiple visits for 692 male participants in the Veterans Affairs Normative Aging Study during 1999–2013. Acceleration was defined using residuals from linear regression of the DNAmPhenoAge on the chronological age. Cumulative smoking (pack-years) was significantly associated with DNAmPhenoAge acceleration, whereas self-reported smoking status was not. We observed significant validated associations between smoking-related loci and DNAmPhenoAge acceleration for 52 CpG sites, where 18 were hypomethylated and 34 were hypermethylated, mapped to 16 genes. The AHRR gene had the most loci (N = 8) among the 16 genes. We generated a smoking aging index based on these 52 loci, which showed positive significant associations with DNAmPhenoAge acceleration. These epigenetic biomarkers may help to predict age-related risks driven by smoking.",
keywords = "Aging acceleration, Aging biomarker, DNA methylation phenotypic age, Smoking-related DNA methylation",
author = "Yang Yang and Xu Gao and Just, {Allan C.} and Elena Colicino and Cuicui Wang and Coull, {Brent A.} and Lifang Hou and Yinan Zheng and Pantel Vokonas and Joel Schwartz and Baccarelli, {Andrea A.}",
year = "2019",
month = "7",
day = "1",
doi = "10.3390/ijerph16132356",
language = "English (US)",
volume = "16",
journal = "International Journal of Environmental Research and Public Health",
issn = "1661-7827",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "13",

}

Smoking-related DNA methylation is associated with DNA methylation phenotypic age acceleration : The veterans affairs normative aging study. / Yang, Yang; Gao, Xu; Just, Allan C.; Colicino, Elena; Wang, Cuicui; Coull, Brent A.; Hou, Lifang; Zheng, Yinan; Vokonas, Pantel; Schwartz, Joel; Baccarelli, Andrea A.

In: International journal of environmental research and public health, Vol. 16, No. 13, 2356, 01.07.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Smoking-related DNA methylation is associated with DNA methylation phenotypic age acceleration

T2 - The veterans affairs normative aging study

AU - Yang, Yang

AU - Gao, Xu

AU - Just, Allan C.

AU - Colicino, Elena

AU - Wang, Cuicui

AU - Coull, Brent A.

AU - Hou, Lifang

AU - Zheng, Yinan

AU - Vokonas, Pantel

AU - Schwartz, Joel

AU - Baccarelli, Andrea A.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - DNA methylation may play a critical role in aging and age-related diseases. DNA methylation phenotypic age (DNAmPhenoAge) is a new aging biomarker and predictor of chronic disease risk. While smoking is a strong risk factor for chronic diseases and influences methylation, its influence on DNAmPhenoAge is unknown. We investigated associations of self-reported and epigenetic smoking indicators with DNAmPhenoAge acceleration in a longitudinal aging study in eastern Massachusetts. DNA methylation was measured in whole blood samples from multiple visits for 692 male participants in the Veterans Affairs Normative Aging Study during 1999–2013. Acceleration was defined using residuals from linear regression of the DNAmPhenoAge on the chronological age. Cumulative smoking (pack-years) was significantly associated with DNAmPhenoAge acceleration, whereas self-reported smoking status was not. We observed significant validated associations between smoking-related loci and DNAmPhenoAge acceleration for 52 CpG sites, where 18 were hypomethylated and 34 were hypermethylated, mapped to 16 genes. The AHRR gene had the most loci (N = 8) among the 16 genes. We generated a smoking aging index based on these 52 loci, which showed positive significant associations with DNAmPhenoAge acceleration. These epigenetic biomarkers may help to predict age-related risks driven by smoking.

AB - DNA methylation may play a critical role in aging and age-related diseases. DNA methylation phenotypic age (DNAmPhenoAge) is a new aging biomarker and predictor of chronic disease risk. While smoking is a strong risk factor for chronic diseases and influences methylation, its influence on DNAmPhenoAge is unknown. We investigated associations of self-reported and epigenetic smoking indicators with DNAmPhenoAge acceleration in a longitudinal aging study in eastern Massachusetts. DNA methylation was measured in whole blood samples from multiple visits for 692 male participants in the Veterans Affairs Normative Aging Study during 1999–2013. Acceleration was defined using residuals from linear regression of the DNAmPhenoAge on the chronological age. Cumulative smoking (pack-years) was significantly associated with DNAmPhenoAge acceleration, whereas self-reported smoking status was not. We observed significant validated associations between smoking-related loci and DNAmPhenoAge acceleration for 52 CpG sites, where 18 were hypomethylated and 34 were hypermethylated, mapped to 16 genes. The AHRR gene had the most loci (N = 8) among the 16 genes. We generated a smoking aging index based on these 52 loci, which showed positive significant associations with DNAmPhenoAge acceleration. These epigenetic biomarkers may help to predict age-related risks driven by smoking.

KW - Aging acceleration

KW - Aging biomarker

KW - DNA methylation phenotypic age

KW - Smoking-related DNA methylation

UR - http://www.scopus.com/inward/record.url?scp=85069268978&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85069268978&partnerID=8YFLogxK

U2 - 10.3390/ijerph16132356

DO - 10.3390/ijerph16132356

M3 - Article

C2 - 31277270

AN - SCOPUS:85069268978

VL - 16

JO - International Journal of Environmental Research and Public Health

JF - International Journal of Environmental Research and Public Health

SN - 1661-7827

IS - 13

M1 - 2356

ER -