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

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The impact of methylation quantitative trait loci (mQTLs) on active smoking-related DNA methylation changes. / Gao, Xu; Thomsen, Hauke; Zhang, Yan; Breitling, Lutz Philipp; Brenner, Hermann.

In: Clinical Epigenetics, Vol. 9, No. 1, 87, 17.08.2017.

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Gao, Xu ; Thomsen, Hauke ; Zhang, Yan ; Breitling, Lutz Philipp ; Brenner, Hermann. / The impact of methylation quantitative trait loci (mQTLs) on active smoking-related DNA methylation changes. In: Clinical Epigenetics. 2017 ; Vol. 9, No. 1.

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TY - JOUR

T1 - The impact of methylation quantitative trait loci (mQTLs) on active smoking-related DNA methylation changes

AU - Gao, Xu

AU - Thomsen, Hauke

AU - Zhang, Yan

AU - Breitling, Lutz Philipp

AU - Brenner, Hermann

PY - 2017/8/17

Y1 - 2017/8/17

N2 - 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.

AB - 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.

KW - Active smoking

KW - DNA methylation

KW - Epigenetic epidemiology

KW - Methylation quantitative trait loci

UR - http://www.scopus.com/inward/record.url?scp=85027488300&partnerID=8YFLogxK

U2 - 10.1186/s13148-017-0387-6

DO - 10.1186/s13148-017-0387-6

M3 - Article

C2 - 28824732

AN - SCOPUS:85027488300

VL - 9

JO - Clinical Epigenetics

JF - Clinical Epigenetics

SN - 1868-7075

IS - 1

M1 - 87

ER -