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

Authors:
Xu Gao
Xu Gao
Harbin Medical University
China
Hauke Thomsen, Dr.
Hauke Thomsen, Dr.
GeneWerk GmbH
Senior Bioinformatician
Bioinformatics, Biostatistics, Genetics
Heidelberg, Baden-Württemberg/Germany | Germany
Yan Zhang
Yan Zhang
Key Laboratory of Food Nutrition and Safety
China
Lutz Philipp Breitling
Lutz Philipp Breitling
Innsbruck Medical University
Austria
Hermann Brenner
Hermann Brenner
German Cancer Research Center (DKFZ)
Germany

Clin Epigenetics 2017 17;9:87. Epub 2017 Aug 17.

Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.

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 (± 50 kb) 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,  = 581; validation set,  = 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.

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.

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http://dx.doi.org/10.1186/s13148-017-0387-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561570PMC

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May 2018
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