The impact of methylation quantitative trait loci (mQTLs) on active smoking-related DNA methylation changes
Autor: | Xu Gao, Lutz P. Breitling, Hauke Thomsen, Hermann Brenner, Yan Zhang |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Male lcsh:QH426-470 Population Quantitative Trait Loci lcsh:Medicine Single-nucleotide polymorphism Quantitative trait locus Biology Polymorphism Single Nucleotide Methylation quantitative trait loci Epigenesis Genetic 03 medical and health sciences Genetics Humans Genetic Predisposition to Disease Epigenetics education Molecular Biology Genetics (clinical) Aged education.field_of_study DNA methylation Epigenetic epidemiology Research Smoking lcsh:R Epigenome Methylation Sequence Analysis DNA Middle Aged Active smoking lcsh:Genetics 030104 developmental biology CpG site CpG Islands Female Developmental Biology |
Zdroj: | Clinical Epigenetics, Vol 9, Iss 1, Pp 1-13 (2017) Clinical Epigenetics |
ISSN: | 1868-7083 1868-7075 |
Popis: | 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, 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. 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. Electronic supplementary material The online version of this article (doi:10.1186/s13148-017-0387-6) contains supplementary material, which is available to authorized users. |
Databáze: | OpenAIRE |
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