The major spur towards the initiation of recent studies of associations between ancestral exposures and their successors concerned a detailed comparison of the survival of individuals born on the edge of the Arctic Circle between 1880 and 1915. Three cohorts of index individuals were identified, based on their years of birth in the village of Őverkalix. Their grandparents’ exposures to famine and/or a harvest glut during their childhoods was identified and the details linked to their grandchildren’s health indices. Detailed analyses highlighted the following: (i) there were strong relationships which were sex-specific, both in regard to the sex of the exposed grandparent and to the sex of the affected index grandchild, and (ii) the exposure effects were specific to particular ages of exposure – the most susceptible period being the ages prior to puberty [Pembrey et al 2006].
This study prompted a number of projects assessing associations between exposures during the pre-pubertal period and health and development of the grandchildren. For example, Van den Berg and Pinger [2016] studied the children and grandchildren of individuals who were exposed to the Berlin famine at ages 8-12. They demonstrated that those whose mothers had been exposed during these ages had worse health outcomes, particularly if they were male. In the subsequent generation, those grandsons whose paternal grandfathers had been exposed prepuberty had higher (better) mental health scores, and granddaughters had higher mental health scores if their maternal grandmothers had experienced the famine during the pre-puberty ages.
Among major cohort studies, information on environmental exposures during the childhood of parents has been collected only occasionally, and that of grandparents rarely. The Avon Longitudinal Study of Parents and Children (ALSPAC) was one pre-birth cohort which had collected information on the ages at which the parents of the study children had started smoking regularly. These data were used to determine whether children whose parents had a history of starting smoking prepuberty were likely to have a different growth pattern than children who started smoking later. We demonstrated that if the fathers had started smoking regularly prior to 11 years of age, their sons (but not their daughters) were more likely to have an increased body mass index (BMI), largely associated with excess fat mass at ages 13, 15 and 17 [Northstone et al 2014]. A subsequent detailed study of antecedents associated with fat mass at age 24 showed that the association remained with paternal smoking <11, and actually increased in size on adjustment [Golding et al 2019]. However, this study also showed an adjusted association between fat mass of the offspring and maternal onset of smoking during puberty (i.e. at ages 11-15).
We have subsequently determined whether the prepubertal ages at starting to smoke regularly of grandparents and/or great-grandparents was also associated with fat mass of the grandchildren and great-grandchildren. We therefore compared the fat mass measurements of the different generations according to whether their ancestors had started smoking pre-puberty with those who started smoking in adolescence (<17). We hypothesised that any effects would differ according to the sex of the smoker, and that of the ancestor. In order to provide a comparison with the results for fat mass, we analysed the results for lean mass, and specifically looked at the outcomes of early onset smoking of the great-grandparents, grandparents and parents on the body composition of the index offspring in late adolescence and early adulthood. The results showed that granddaughters, but not grandsons, whose paternal grandfather started smoking pre-puberty were significantly fatter than those whose paternal grandfather started smoking between ages 13 and 16. There were similar associations with the great-granddaughters (but not great-grandsons) of fathers of maternal grandfathers who had started smoking pre-puberty [Golding et al 2022].
This programme of research is ongoing, with inter- and transgenerational research into the associations of different phenotypes with ancestral stressors and with ancestral smoking habits. See Table 1 in Useful Illustrations for a summary of findings to date in regard to the grandmother smoking during pregnancy.
van den Berg, G.J. & Pinger, P.R. (2016) Transgenerational effects of childhood conditions on third generation health and education outcomes. Econ. Hum. Biol. 23, 103-120.