Advanced

The impact of methylation quantitative trait loci (mQTLs) on active smoking-related DNA methylation changes

Gao, Xu; Thomsen, Hauke LU ; Zhang, Yan; Breitling, Lutz Philipp and Brenner, Hermann (2017) In Clinical Epigenetics 9(1).
Abstract

Background: Methylation quantitative trait loci (mQTLs) are the genetic variants that may affect the DNA methylation patterns of CpG sites. However, their roles in influencing the disturbances of smoking-related epigenetic changes have not been well established. This study was conducted to address whether mQTLs exist in the vicinity of smoking-related CpG sites (±50kb) and to examine their associations with smoking exposure and all-cause mortality in older adults. Results: We obtained DNA methylation profiles in whole blood samples by Illumina Infinium Human Methylation 450 BeadChip array of two independent subsamples of the ESTHER study (discovery set, n=581; validation set, n=368) and their corresponding genotyping data using the... (More)

Background: Methylation quantitative trait loci (mQTLs) are the genetic variants that may affect the DNA methylation patterns of CpG sites. However, their roles in influencing the disturbances of smoking-related epigenetic changes have not been well established. This study was conducted to address whether mQTLs exist in the vicinity of smoking-related CpG sites (±50kb) and to examine their associations with smoking exposure and all-cause mortality in older adults. Results: We obtained DNA methylation profiles in whole blood samples by Illumina Infinium Human Methylation 450 BeadChip array of two independent subsamples of the ESTHER study (discovery set, n=581; validation set, n=368) and their corresponding genotyping data using the Illumina Infinium OncoArray BeadChip. After correction for multiple testing (FDR), we successfully identified that 70 out of 151 previously reported smoking-related CpG sites were significantly associated with 192 SNPs within the 50kb search window of each locus. The 192 mQTLs significantly influenced the active smoking-related DNA methylation changes, with percentage changes ranging from 0.01 to 18.96%, especially for the weakly/moderately smoking-related CpG sites. However, these identified mQTLs were not directly associated with active smoking exposure or all-cause mortality. Conclusions: Our findings clearly demonstrated that if not dealt with properly, the mQTLs might impair the power of epigenetic-based models of smoking exposure to a certain extent. In addition, such genetic variants could be the key factor to distinguish between the heritable and smoking-induced impact on epigenome disparities. These mQTLs are of special importance when DNA methylation markers measured by Illumina Infinium assay are used for any comparative population studies related to smoking-related cancers and chronic diseases.

(Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
keywords
Active smoking, DNA methylation, Epigenetic epidemiology, Methylation quantitative trait loci
in
Clinical Epigenetics
volume
9
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85027488300
ISSN
1868-7075
DOI
10.1186/s13148-017-0387-6
language
English
LU publication?
no
id
43a0c2df-eef9-47eb-a386-dad6b7b8a914
date added to LUP
2017-10-26 08:59:05
date last changed
2018-01-07 12:23:37
@article{43a0c2df-eef9-47eb-a386-dad6b7b8a914,
  abstract     = {<p>Background: Methylation quantitative trait loci (mQTLs) are the genetic variants that may affect the DNA methylation patterns of CpG sites. However, their roles in influencing the disturbances of smoking-related epigenetic changes have not been well established. This study was conducted to address whether mQTLs exist in the vicinity of smoking-related CpG sites (±50kb) and to examine their associations with smoking exposure and all-cause mortality in older adults. Results: We obtained DNA methylation profiles in whole blood samples by Illumina Infinium Human Methylation 450 BeadChip array of two independent subsamples of the ESTHER study (discovery set, n=581; validation set, n=368) and their corresponding genotyping data using the Illumina Infinium OncoArray BeadChip. After correction for multiple testing (FDR), we successfully identified that 70 out of 151 previously reported smoking-related CpG sites were significantly associated with 192 SNPs within the 50kb search window of each locus. The 192 mQTLs significantly influenced the active smoking-related DNA methylation changes, with percentage changes ranging from 0.01 to 18.96%, especially for the weakly/moderately smoking-related CpG sites. However, these identified mQTLs were not directly associated with active smoking exposure or all-cause mortality. Conclusions: Our findings clearly demonstrated that if not dealt with properly, the mQTLs might impair the power of epigenetic-based models of smoking exposure to a certain extent. In addition, such genetic variants could be the key factor to distinguish between the heritable and smoking-induced impact on epigenome disparities. These mQTLs are of special importance when DNA methylation markers measured by Illumina Infinium assay are used for any comparative population studies related to smoking-related cancers and chronic diseases.</p>},
  articleno    = {87},
  author       = {Gao, Xu and Thomsen, Hauke and Zhang, Yan and Breitling, Lutz Philipp and Brenner, Hermann},
  issn         = {1868-7075},
  keyword      = {Active smoking,DNA methylation,Epigenetic epidemiology,Methylation quantitative trait loci},
  language     = {eng},
  month        = {08},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {Clinical Epigenetics},
  title        = {The impact of methylation quantitative trait loci (mQTLs) on active smoking-related DNA methylation changes},
  url          = {http://dx.doi.org/10.1186/s13148-017-0387-6},
  volume       = {9},
  year         = {2017},
}