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)
- author
- Gao, Xu
; Thomsen, Hauke
LU
; Zhang, Yan
; Breitling, Lutz Philipp
and Brenner, Hermann
- publishing date
- 2017-08-17
- 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
- article number
- 87
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:28824732
- 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
- 2024-03-16 02:53:18
@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>}},
author = {{Gao, Xu and Thomsen, Hauke and Zhang, Yan and Breitling, Lutz Philipp and Brenner, Hermann}},
issn = {{1868-7075}},
keywords = {{Active smoking; DNA methylation; Epigenetic epidemiology; Methylation quantitative trait loci}},
language = {{eng}},
month = {{08}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
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}},
doi = {{10.1186/s13148-017-0387-6}},
volume = {{9}},
year = {{2017}},
}