Abstract
BackgroundMethylation 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 (± 50 kb) and to examine their associations with smoking exposure and all-cause mortality in older adults.ResultsWe 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 50 kb 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.ConclusionsOur 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.
Highlights
Methylation quantitative trait loci are the genetic variants that may affect the DNA methylation patterns of CpG sites
We found the DNA methylation levels of 70 CpG sites to be influenced by 192 proximal single nucleotide polymorphisms (SNPs)
Together with previous studies [8, 23], we suggest that future investigations utilizing smoking-related CpG sites might need to take the genotypes, especially the Methylation quantitative trait loci (mQTLs) of less robustly smoking-related loci, into consideration to account for their potential impact on DNA methylation levels
Summary
Methylation quantitative trait loci (mQTLs) are the genetic variants that may affect the DNA methylation patterns of CpG sites Their roles in influencing the disturbances of smoking-related epigenetic changes have not been well established. In 2016, Gonseth et al found out that three of the strongest maternal smoking-related CpG sites in newborns were significantly associated with SNPs located in the vicinity of each gene [23] These hereditary traits provide a possible mechanism by which methylation patterns could be different under environmental exposures, if the distribution of risk alleles differs between the exposed and the unexposed. The linkages of epigenetic signatures to genotypes might further provide more mechanistic evidence on the genetic and environmental risk factors for various forms of diseases [24]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
