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

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title = "The impact of methylation quantitative trait loci (mQTLs) on active smoking-related DNA methylation changes",
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 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.",
keywords = "Active smoking, DNA methylation, Epigenetic epidemiology, Methylation quantitative trait loci",
author = "Xu Gao and Hauke Thomsen and Yan Zhang and Breitling, {Lutz Philipp} and Hermann Brenner",
year = "2017",
month = aug,
day = "17",
doi = "10.1186/s13148-017-0387-6",
language = "English",
volume = "9",
journal = "Clinical Epigenetics",
issn = "1868-7075",
publisher = "BioMed Central (BMC)",
number = "1",