Does genetic variation at candidate genomic regions influence the molecular response to smoking?

Abstract

Background- Tobacco smoking is a major disease risk factor. Studies have linked smoking to multiple types of cancer and efforts to unravel the complexities of cancer have uncovered the contribution of epigenetic factors such as DNA methylation. As expected, Smoking has also been shown to have a huge impact on DNA methylation. Previous studies have linked hypomethylation in multiple CpGs to smoking. However not much is known about the contributions of genotype to this molecular response to smoking. Hence, the aim of this study is to examine if the effect of smoking on DNA methylation at the candidate gene is influenced by genetic variation. Methods and Results- Candidate CpG related to smoking were extracted from the previous study and the Linear Mixed Effects model method was employed to confirm their association with smoking in the TwinsUK data. The effect of genotype and genotype-smoking was then studied in the significant CpGs by the same model method using candidate meQTLs from the GoDMC meQTLs data. Twenty-six CpGs with significant association to smoking were discovered out of which 12 were novel associations. Thirty-one CpG-meQTLs with significant association were found while only one significant genotype-smoking interaction was uncovered. Conclusion- The result of the study shows that genotype contributes significantly to the observed variation in DNA methylation at certain loci.