The great-granddaughters of men who smoked cigarettes when they were pre-pubescent boys are more likely to carry excess fat on their bodies as young women several decades later, a rather startling study has found.
The discovery – which scientists claim is one of the "first human demonstrations of transgenerational effects of an environmental exposure across four generations" – suggests ancestral exposures to things like tobacco smoke may have consequences that linger within families undetected for entire generations.
"If these associations are confirmed in other datasets, this will be one of the first human studies with data suitable to start to look at these associations and to begin to unpick the origin of potentially important cross-generation relationships," says epidemiologist Jean Golding from Bristol University in the UK.
In 2014, Golding and fellow researchers assessed data from the Avon Longitudinal Study of Parents and Children (aka, the 'Children of the 90s' study), an observational study of pregnant women and their families, which began in the early 1990s and was initially led by Golding.
The 2014 analysis of questionnaire data from the Children of the 90s study revealed that the sons of fathers who started smoking before they were 11 years old were more likely to have a higher body mass index (BMI) in adolescence, with increased average waist circumference and whole-body fat mass.
This, Golding and her co-authors wrote, was a rare example of a non-genetic transgenerational signal inherited by human offspring, with much of the existing evidence of the effects of ancestral exposures coming from studies involving animal models.
Now, a deeper dive into the Children of the 90s dataset reveals the phenomenon extends even further across generations, and not just from a father to his son, but from a grandfather to his granddaughter, and also from a great-grandfather to his great-granddaughter.
"We now show that if the paternal grandfather had started smoking pre-puberty [younger than 13], compared with later in childhood (13–16 years), his granddaughters, but not grandsons, had evidence of excess fat mass at two ages [17 and 24 years of age]," the researchers explain in their new paper.
"When fathers of maternal grandfathers had started smoking pre-puberty, their great-granddaughters, but not great-grandsons, had excess body fat [at 17 and 24]."
The researchers say a similar effect can be seen even when the intervening generations don't smoke regularly while under 13 years of age, evidencing a transgenerational effect across four generations.
"Before puberty, exposure of a boy to particular substances might have an effect on generations that follow him," Golding says, noting that one of the important takeaways of the finding is the implications it has for our understanding of people's health today, and how it may be shaped by unseen influences.
"One of the reasons why children become overweight may be not so much to do with their current diet and exercise, rather than the lifestyle of their ancestors or the persistence of associated factors over the years."
The team says we'll need a lot more research into this phenomenon to understand what's going on here, and acknowledge that their own analysis has a number of limitations, including that there was a large amount of missing data in terms of respondents' awareness of the childhoods and circumstances of their parents and grandparents.
Nonetheless, they do claim their study offers first-of-its-kind evidence of transgenerational effects, although quite how those effects arise is still very much unknown at this point.
It's possible this is just a correlation somehow, not an effect caused by exposure to tobacco smoke; the researchers acknowledge it's loosely possible that the pre-puberty smokers in the study may have had a hereditary predisposition to obesity that only surfaced a few generations downstream.
"It is noteworthy that the associations indicated are related to obesity; it is generally recognized that obesity is a complex disorder caused by the interplay of genetics, epigenetics, and environmental factors," the researchers conclude.
"However, before hypotheses are generated as to the mechanisms by which the effects we have shown may have occurred, it is important to seek confirmatory evidence from other studies."
The findings are reported in Scientific Reports.