Abstract
Mechanistic research suggests that lifestyle and environmental factors impact respiratory health across generations by epigenetic changes transmitted through male germ cells. Evidence from studies on humans is very limited.
We investigated multi-generation causal associations to estimate the causal effects of tobacco smoking on lung function within the paternal line. We analysed data from 383 adult offspring (age: 18–47; female: 52.0%) and their 274 fathers, who had participated in the ECRHS/RHINESSA generation study and had provided valid measures of pre-bronchodilator lung function. Two counterfactual-based, multi-level mediation models were developed with: paternal grandmothers’ smoking in pregnancy and fathers’ smoking initiation in prepuberty as exposures; fathers’ FEV1 and FVC, or FEV1/FVC z-scores as potential mediators (proxies of unobserved biological mechanisms that are true mediators); offspring's FEV1 and FVC, or FEV1/FVC z-scores as outcomes. All effects were summarised as differences in expected z-scores related to fathers’ and grandmothers’ smoking history.
Fathers’ smoking initiation in prepuberty had a negative direct effect on both offspring's FEV1 (−0.36; 95% confidence interval: −0.63, −0.10) and FVC (−0.50; −0.80, −0.20) compared to fathers’ never smoking. Paternal grandmothers’ smoking in pregnancy had a negative direct effect on fathers’ FEV1/FVC (−0.57; −1.09, −0.05) and a negative indirect effect on offspring's FEV1/FVC (−0.12; −0.21, −0.03) compared to grandmothers’ not smoking before fathers’ birth nor during fathers’ childhood.
Fathers’ smoking in prepuberty and paternal grandmothers’ smoking in pregnancy may cause lower lung function in offspring. Our results support the concept that lifestyle-related exposures during these susceptibility periods influence the health of future generations.
Footnotes
This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.
Conflict of interest: Prof. Accordini has nothing to disclose.
Conflict of interest: Dr. Calciano has nothing to disclose.
Conflict of interest: Dr. Johannessen has nothing to disclose.
Conflict of interest: Dr. Benediktsdóttir has nothing to disclose.
Conflict of interest: Dr. Bertelsen has nothing to disclose.
Conflict of interest: Dr. Bråbäck has nothing to disclose.
Conflict of interest: Dr. Dharmage has nothing to disclose.
Conflict of interest: Dr. Forsberg has nothing to disclose.
Conflict of interest: Dr. Gómez Real has nothing to disclose.
Conflict of interest: Dr. Holloway reports grants from European Union's Horizon 2020 research and innovation programme, grants from Research Council of Norway, during the conduct of the study.
Conflict of interest: Dr. Holm has nothing to disclose.
Conflict of interest: Dr. Janson has nothing to disclose.
Conflict of interest: Dr. Jõgi has nothing to disclose.
Conflict of interest: Dr. Rain Jõgi reports grants from Estonian Research Council Personal Research Grant no 562, during the conduct of the study; personal fees from Consultancy, grants from Grants/grants pending, personal fees from Payment for lectures, personal fees from Travel/acco
Conflict of interest: Dr. Malinovschi has nothing to disclose.
Conflict of interest: Dr. Marcon has nothing to disclose.
Conflict of interest: Dr. Martínez-Moratalla Rovira has nothing to disclose.
Conflict of interest: Dr. Sánchez-Ramos has nothing to disclose.
Conflict of interest: Dr. Schlünssen has nothing to disclose.
Conflict of interest: Dr. Torén has nothing to disclose.
Conflict of interest: Professor. Jarvis reports grants from EU, during the conduct of the study; .
Conflict of interest: Dr. Svanes has nothing to disclose.
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- Received July 15, 2020.
- Accepted March 11, 2021.
- Copyright ©The authors 2021. For reproduction rights and permissions contact permissions{at}ersnet.org
