Genes linked to smoking in pregnancy identified: Sons face greater risks microbiologystudy

Researchers at the University of Aberdeen have identified a genetic link to smoking in pregnancy. Results from the U.K.-wide study also showed that males experience more long-lasting effects when the mother smokes while pregnant (maternal smoking) than females—including dying younger if they go on to smoke themselves.

In one of the world’s largest ever studies into the effects of maternal smoking, researchers from the University of Aberdeen studied more than half a million individuals to understand the effects of smoking in pregnancy and how these can persist throughout adulthood. The paper is published today in eBiomedicine.

The team, led by Professor Paul Fowler, chair in translational medical sciences at the University of Aberdeen, used the genetic relationship between mothers and their adult children to conduct the first large-scale genetic analysis of maternal smoking. They found several gene variants that increase the likelihood of maternal smoking, opening up potential new avenues for targeted smoking cessation treatments.

Using samples from the UK Biobank, data from 500,000 individuals across 22 centers in Scotland, England and Wales, the team were able to investigate the genetic, biochemical and socio-demographic factors associated with smoking during pregnancy.

They found that at every stage, male fetuses and adult sons are more affected by maternal smoking during pregnancy than females. This manifested as changes in levels of various genes in male fetal livers as early as 17 weeks pregnant right through to adult males having shorter life expectancy.

Fundamentally, the authors stress that, if the adult man stops smoking, or did not smoke at all, they can counter these risks.

The increased likelihood for an early death was reduced in men who reported to have never smoked cigarettes themselves. This new insight could help devise new and more effective strategies to mitigate the adverse effects of maternal smoking exposure. For example, specifically targeting the children of smokers in smoking cessation health campaigns and screening mothers who are smokers for the presence of smoking addiction-related gene variants to target those individuals for additional counseling.

The study also found that men were more likely to develop cancer in adulthood and are more susceptible to developing type 2 diabetes than females.

Women, however, were more likely to develop digestive and reproductive disorders as well as mental health issues.

Postgraduate researcher Mihail Mihov who conducted the research as part of their Ph.D. studies explains, “Maternal smoking during pregnancy has been linked to many health issues for babies. However, we previously had limited knowledge about which processes in the womb are influenced by maternal smoking and how they translate to diminished health later in life.

“Our findings show that maternal smoking impacts baby’s health, particularly for males, from as early as the second trimester and this continues throughout adulthood.

“However, we did find that this can be somewhat reversed. Our results indicate that smoking cessation or, ideally, not smoking at all in men can counter the increased risk of early death in adulthood.

“We also, for the first time, identified several gene variants which increase the likelihood that a mother will smoke or be addicted to smoking, even during pregnancy.

“This opens avenues where we can look for potentially gene-specific targetable pathways to smoking cessation and therefore offer ways to decrease the societal burden of maternal smoking in our aging society.”

Felix Grassmann, professor of epidemiology and biostatistics at the Health and Medical University, Potsdam, Germany, who co-led the research added, “Most research has been conducted in cohorts with too few individuals thus lacking statistical power to uncover the rarer associations. In this research, we used the UK Biobank cohort which has genetic, biochemistry and medical questionnaire data on more than 500,000 individuals, making it one of the biggest studies reported on the effects of maternal smoking during pregnancy.

“In short, we found that when a mother smokes during pregnancy her son’s liver is more affected than her daughter’s liver. This difference and the sex difference in risk of death continues into middle age.”

Professor Paul Fowler added, “We hope our findings will pave the way towards investigating the molecular effects of maternal smoking which will allow the scientific community to uncover the specific mechanisms by which the trait modifies or initiates specific diseases.

“Ultimately, we also hope it helps the medical community to develop even better counseling strategies and campaigns towards smoking cessation.”

Sheila Duffy, chief executive of the UK health charity Action on Smoking and Health Scotland (ASH Scotland), said, “We welcome this research as its world leading insights are valuable and will help to better inform parents and communities about exposure to tobacco during pregnancy harming not only the mother and baby, but also spotlighting that the harmful impacts persist into seriously damaging children’s lives into adulthood.

“Tobacco is utterly toxic and it is vital that we support people to move away from it, something many parents are especially keen to do during pregnancy. This study shows that tobacco toxins damage genes and human development in ways we are only starting to understand.

“Smoking rates are especially high in communities where people are facing multiple social and economic pressures. This is why through the strongest possible measures enabled by the passing of the four-nations Tobacco and Vapes Bill are important to push back on the damaging grip that tobacco and related products industries are having in our society.

“It is time for profit-focused tobacco companies to be held to account for the health damage their products are doing to people’s lives, and we must ensure all people who smoke, including those who are pregnant, have access to specialist quit smoking support delivered by qualified health service professionals.”

John Waldron, policy and public affairs manager at the UK health charity Action on Smoking and Health (ASH) said, “This study highlights the importance of supporting every woman to have a smokefree pregnancy. It’s particularly concerning to see such an elevated risk of early death among men, who we know are more likely to smoke.

“The generational smoking ban could mean around 10,000 fewer women in England are smoking at the start of their pregnancy by 2033, with a similar impact in the other U.K. nations. However, this will not impact adults who already smoke and more support is needed to help them quit.

“The UK Government is currently rolling out a financial incentive scheme to support pregnant women in England to quit smoking. However, funding for this has not been confirmed beyond March 2025. We urge the Government to extend this scheme to help give every child a smokefree start in life.”