Teen Smokers Have Increased Risk of Passing on Asthma Traits in Fatherhood, Study Finds

Epigenetic changes in sites mapped to genes in children of fathers who smoked before the age of 15 years, suggests how fathers’ early teenage smoking may increase the risk of their future children developing asthma, obesity, and low lung function.

Smoking

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The study suggests how epigenetic mechanisms of pubertal paternal smoking may increase the risk of respiratory health across generations transmitted specifically through male germ cells.

To the researcher’s knowledge, this epigenome-wide association study (EWAS), published in Clinical Epigenetics¹ is the first of its kind to investigate the impact of fathers’ smoking in their teenage years on their offspring.

“Our studies in the large international RHINESSA, RHINE and ECRHS studies have shown that the health of future generations depends on the actions and decisions made by young people today – long before they are parents – in particular for boys in early puberty and mothers/grandmothers both pre-pregnancy and during pregnancy,” Cecilie Svanes, MD, PhD, from the University of Bergen and Research Director of the RHINESSA study, said in a statement.² “It is really exciting that we have now been able to identify a mechanism that explains our observations in the cohorts.”

The EWAS study in the RHINESSA cohort included epigenetic profiles of 875 individuals between the ages 7 and 50 years, and the smoking behaviors of their fathers. The research was conducted at the University of Southampton and the University of Bergen in Norway. From this cohort, 304 fathers had pubertal onset smoking at younger than 15 years.

DNA methylation in offspring was measured using 1μg of DNA extracted from peripheral blood, using a simple salting out procedure. Both sensitivity and replication analyses were performed. These changes in methylation are known to regulate gene expression and are associated with asthma, obesity, and wheezing.

The analysis included EWAS on preconception father’s smoking exposure with DNA methylation using robust multiple linear regression models. The researchers also adjusted for offspring age, own smoking, and maternal smoking. Personal smoking was defined as current, former, or never smoking, with maternal smoking defined by reports of mother’s smoking during their childhood and during pregnancy.

After analysis, the researchers found father’s smoking prior to preconception was associated with methylation of blood DNA in offspring at 2 cytosine-phosphate-guanine sites (CpGs) in PRR5 and CENPP (false discovery rate [FDR] < 0.05.)

Furthermore, 19 epigenetic changes were found at 19 sites mapped to 14 genes (TLR9, DNTT, FAM53B, NCAPG2, PSTPIP2, MBIP, C2orf39, NTRK2, DNAJC14, CDO1, PRAP1, TPCN1, IRS1 and CSF1R) in the children of fathers who smoked before the age of 15 years. Some of these sites were associated with offspring outcomes, including ever-asthma (NTRK2), ever-wheezing (DNAJC14, TPCN1), weight (FAM53B, NTRK2) and BMI (FAM53B, NTRK2) (P < .05).

The researchers acknowledged some limitations to the study, including the effects of second-hand smoking exposure, self-reported smoking bias, and the likelihood that reporting of fathers’ smoking habits is independent of DNA methylation observed in offspring.

Despite these limitations, the researchers believe the study shows how fathers smoking in teenage years has serious health implications for their future children, and that this association may transmute into other health challenges with the increase of teenage vaping and nicotine use.

“The evidence from this study comes from people whose fathers smoked as teenagers in the 60s and 70s, when smoking tobacco was much more common,” John Holloway, PhD, FHEA, the University of Southampton and the National Institute for Research Health Southampton Biomedical Research Centre, said in a statement.² "We can’t definitely be sure vaping will have similar effects across generations, but we shouldn’t wait a couple of generations to prove what impact teenage vaping might have. We need to act now.”

References

1. Kitaba NT, Knudsen GT, Johannessen A, et al. Fathers’ preconception smoking and offspring DNA methylation. Clinical Epigenetics. 2023;15(1). doi:10.1186/s13148-023-01540-7

2. University of Southampton. Boys who smoke in their early teens risk passing on harmful epigenetic traits to future children. EurekAlert! August 30, 2023. Accessed September 11, 2023. https://www.eurekalert.org/news-releases/999962.