TY - JOUR
T1 - Longitudinal analysis of epigenome-wide DNA methylation reveals novel smoking-related loci in African Americans
AU - Liu, Jiaxuan
AU - Zhao, Wei
AU - Ammous, Farah
AU - Turner, Stephen T.
AU - Mosley, Thomas H.
AU - Zhou, Xiang
AU - Smith, Jennifer A.
N1 - Publisher Copyright:
© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2019/2/1
Y1 - 2019/2/1
N2 - Changes in DNA methylation may be a potential mechanism that mediates the effects of smoking on physiological function and subsequent disease risk. Given the dynamic nature of the epigenome, longitudinal studies are indispensable for investigating smoking-induced methylation changes over time. Using blood samples collected approximately five years apart in 380 African Americans (mean age 60.7 years) from the Genetic Epidemiology Network of Arteriopathy (GENOA) study, we measured DNA methylation levels using Illumina HumanMethylation BeadChips. We evaluated the association between Phase 1 smoking status and rate of methylation change, using generalized estimating equation models. Among the 6958 CpG sites examined, smoking status was associated with methylation change for 22 CpGs (false discovery rate q < 0.1), with the majority (91%) becoming less methylated over time. Methylation change was greater in ever smokers than never smokers, and the absolute differences in rates of change ranged from 0.18 to 0.77 per decade in M value, equivalent to a β value change of 0.013 to 0.047 per decade. Significant enrichment was observed for CpG islands, enhancers, and DNAse hypersensitivity sites (p < 0.05). Although biological pathway analyses were not significant, most of the 22 CpGs were within genes known to be associated with cardiovascular disease, cancers, and aging. In conclusion, we identified epigenetic signatures for cigarette smoking that may have been missed in cross-sectional analyses, providing insight into the epigenetic effect of smoking and highlighting the importance of longitudinal analysis in understanding the dynamic human epigenome.
AB - Changes in DNA methylation may be a potential mechanism that mediates the effects of smoking on physiological function and subsequent disease risk. Given the dynamic nature of the epigenome, longitudinal studies are indispensable for investigating smoking-induced methylation changes over time. Using blood samples collected approximately five years apart in 380 African Americans (mean age 60.7 years) from the Genetic Epidemiology Network of Arteriopathy (GENOA) study, we measured DNA methylation levels using Illumina HumanMethylation BeadChips. We evaluated the association between Phase 1 smoking status and rate of methylation change, using generalized estimating equation models. Among the 6958 CpG sites examined, smoking status was associated with methylation change for 22 CpGs (false discovery rate q < 0.1), with the majority (91%) becoming less methylated over time. Methylation change was greater in ever smokers than never smokers, and the absolute differences in rates of change ranged from 0.18 to 0.77 per decade in M value, equivalent to a β value change of 0.013 to 0.047 per decade. Significant enrichment was observed for CpG islands, enhancers, and DNAse hypersensitivity sites (p < 0.05). Although biological pathway analyses were not significant, most of the 22 CpGs were within genes known to be associated with cardiovascular disease, cancers, and aging. In conclusion, we identified epigenetic signatures for cigarette smoking that may have been missed in cross-sectional analyses, providing insight into the epigenetic effect of smoking and highlighting the importance of longitudinal analysis in understanding the dynamic human epigenome.
KW - DNA methylation
KW - Smoking
KW - epigenome-wide association study
KW - longitudinal analysis
UR - http://www.scopus.com/inward/record.url?scp=85062958241&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062958241&partnerID=8YFLogxK
U2 - 10.1080/15592294.2019.1581589
DO - 10.1080/15592294.2019.1581589
M3 - Article
C2 - 30764717
AN - SCOPUS:85062958241
SN - 1559-2294
VL - 14
SP - 171
EP - 184
JO - Epigenetics
JF - Epigenetics
IS - 2
ER -