Effect of tobacco smoking on the epigenetic age of human respiratory organs

Abstract

BackgroundSmoking leads to the aging of organs. However, no studies have been conducted to quantify the effect of smoking on the aging of respiratory organs and the aging-reversing ability of smoking cessation.ResultsWe collected genome-wide methylation datasets of buccal cells, airway cells, esophagus tissue, and lung tissue from non-smokers, smokers, and ex-smokers. We used the “epigenetic clock” method to quantify the epigenetic age acceleration in the four organs. The statistical analyses showed the following: (1) Smoking increased the epigenetic age of airway cells by an average of 4.9 years and lung tissue by 4.3 years. (2) After smoking ceased, the epigenetic age acceleration in airway cells (but not in lung tissue) slowed to a level that non-smokers had. (3) The epigenetic age acceleration in airway cells and lung tissue showed no gender difference.ConclusionsSmoking can accelerate the epigenetic age of human respiratory organs, but the effect varies among organs and can be reversed by smoking cessation. Our study provides a powerful incentive to reduce tobacco consumption autonomously.

Simulating ComBat: how batch correction can lead to the systematic introduction of false positive results in DNA methylation microarray studies

“…The resulting data from our simulation share many properties with their biological CpG counterparts, such as the distribution of differences in type-I and type-II CpGsites which occur in Illumina arrays for technical reasons [25]. 3 This enabled us to follow the ChAMP pipeline as planned and in the next step to normalize the data for type-I and type-II differences, as required by the manual for the sva package [21] using the beta-mixture quantile normalization (BMIQ) method [26]. BMIQ serves as an intra-sample normalization procedure, correcting the deviation of type-II probe values, and is implemented within the "champ.norm" function.…”

“…In a second simulation, the number of batch factors was increased with two equal-sized randomly distributed factor levels each. In a second simulation, we investigated the effect of increasing the sample size in five steps from n = 96 (one samples plate / 8 chips) up to 2 Data and the R code for the simulation are available as a Supplementary Material (MethylationSimulationScript.ZIP) 3 A more thorough description of the simulation and the resulting simulated value distributions can be found in Supplementary Document -Section B n = 768 samples. After these simulations with respect to the Illumina EPIC array containing 850,000 CpG-sites, the effects of ComBat on older and smaller arrays (Illumina Infinium HumanMethylation27 BeadChip (27 K) and 450 K) with n = 96 samples were examined.…”

“…In the last two decades, the field of epigenetics has opened up new perspectives on complex medical questions [1][2][3]. DNA methylation (DNAm) is assumed to be modulated both by heritable factors [4] and by environmental conditions [5,6].…”

Incorporating multiple sets of eQTL weights into gene‐by‐environment interaction analysis identifies novel susceptibility loci for pancreatic cancer

“…TRIP10 , whose overexpression may enhance pancreatic cancer cell migration, could be involved in the carcinogenesis of pancreatic cancer (Roignot et al, 2010). Smoking could increase the methylation levels in the upstream of TRIP10 and thus upregulate its expression (Walters et al, 2014; X. Wu et al, 2019). To our knowledge, these two genes have not been reported to interact with cigarette smoking.…”

Epigenetic Alteration Shaped by the Environmental Chemical Bisphenol A

“…New and ongoing studies are continuously revealing the role of epigenetics in human disorders and fatal diseases linked to environmental exposure, including endocrine disruptors (BPA, DDT, phthalates; Dutta et al, 2020 ); tobacco smoke ( Wu et al, 2019 ); diesel exhaust particles, such as PM2.5 and PM10; heavy metals, such as arsenic, nickel, and lead ( Wang et al, 2020 ); and other indoor and outdoor pollutants ( Mileva et al, 2014 ; Zhu et al, 2018 ; Freeman et al, 2020 ). A systematic review summarized that BPA has many effects, such as hormonal alterations, alteration of male reproductive organs, and epigenetic changes involving the male reproductive system ( Cariati et al, 2020 ).…”