Effects of maternal and paternal smoking on offspring cardiometabolic risk factors in adulthood: a multi-method intergenerational Mendelian randomization study.
14 affiliations
- 1MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK. [email protected].
- 2Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. [email protected].
- 3Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia. [email protected].
- 4MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK.
- 5Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
- 6Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
- 7Frazer Institute, University of Queensland, Woolloongabba, QLD, Australia.
- 8Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
- 9HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, NTNU Norwegian University of Science and Technology, Trondheim, Norway.
- 10HUNT Research Centre, Department of Public Health and Nursing, NTNU Norwegian University of Science and Technology, Levanger, Norway.
- 11Department of Endocrinology, Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, 7030, Norway.
- 12Clinic of Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
- 13Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
- 14NIHR Bristol Biomedical Research Centre Bristol, University Hospitals Bristol and Weston NHS Foundation Trust, University of Bristol, Bristol, UK.
Abstract
Background
Parental smoking has been linked to several adverse offspring cardiometabolic outcomes; however, evidence is conflicting regarding the causal and long-term nature of these associations.Methods
We investigated the effects of maternal and paternal smoking, capturing exposure before, during, and after pregnancy, on eleven offspring cardiometabolic risk factors related to body composition, blood pressure, glucose, and lipid levels in adulthood. We applied a multi-method intergenerational Mendelian randomization (MR) framework, combining two-sample MR (outcome GWAS, n = up to 564,160) and one-sample MR analyses (n = up to 17,484 genotyped mother-father-offspring trios with offspring cardiometabolic risk factors) from the HUNT cohort, Norway, and the UK Biobank and ALSPAC cohorts in the United Kingdom. Smoking behaviour was instrumented using genome-wide significant variants for smoking initiation and heaviness from large genome-wide association studies (2019 and 2022), with additional analyses of the CHRNA5 variant rs16969968.Results
Using the two-sample MR approach, we found an average change in adult offspring waist-hip ratio (WHR) per one standard deviation (SD) increase in maternal cigarettes smoked per day of 0.25 SD (95% CI: 0.13, 0.38; 2019 GWAS), 0.19 SD (95% CI: 0.08, 0.31; 2022 GWAS) and 0.27 SD (95% CI: 0.07, 0.47; CHRNA5 rs16969968). We also found tentative evidence of comparable effects on offspring body mass index and C-reactive protein. One-sample MR analyses using CHRNA5 rs16969968, restricted to maternal ever-smokers, provided supporting evidence consistent with the primary findings for maternal smoking heaviness on offspring WHR. We found little evidence that maternal smoking initiation affected WHR, and little evidence that maternal smoking heaviness affected the remaining cardiometabolic risk factors; paternal smoking showed no clear effect on any outcome. Results from sensitivity analyses were consistent with these main findings.Conclusions
Adult offspring of mothers with a propensity to heavier smoking exhibited greater central adiposity, a phenotype associated with increased cardiometabolic risk. These findings are consistent with a causal influence of maternal smoking heaviness across the preconception, perinatal, and postnatal periods on later-life offspring body fat distribution. Further triangulation using alternative causal approaches is warranted.
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BibTeX
@article{power2026effects,
title = {{Effects of maternal and paternal smoking on offspring cardiometabolic risk factors in adulthood: a multi-method intergenerational Mendelian randomization study.}},
author = {Grace M Power and Tom A Bond and Laxmi Bhatta and Bjørn Olav Åsvold and Ben Brumpton and Giulio Centorame and Gibran Hemani and Deborah A Lawlor and Geng Wang and Nicole Warrington and David M Evans and Gunn-Helen Moen and George Davey Smith},
journal = {BMC medicine},
year = {2026},
month = aug,
doi = {10.1186/s12916-026-05065-7},
url = {https://europepmc.org/article/MED/42972375},
note = {CC BY},
}
RIS
TY - JOUR
TI - Effects of maternal and paternal smoking on offspring cardiometabolic risk factors in adulthood: a multi-method intergenerational Mendelian randomization study.
AU - Grace M Power
AU - Tom A Bond
AU - Laxmi Bhatta
AU - Bjørn Olav Åsvold
AU - Ben Brumpton
AU - Giulio Centorame
AU - Gibran Hemani
AU - Deborah A Lawlor
AU - Geng Wang
AU - Nicole Warrington
AU - David M Evans
AU - Gunn-Helen Moen
AU - George Davey Smith
PY - 2026
DA - 2026/08/05
JO - BMC medicine
DO - 10.1186/s12916-026-05065-7
UR - https://europepmc.org/article/MED/42972375
AB - Background Parental smoking has been linked to several adverse offspring cardiometabolic outcomes; however, evidence is conflicting regarding the causal and long-term nature of these associations.Methods We investigated the effects of maternal and paternal smoking, capturing exposure before, during, and after pregnancy, on eleven offspring cardiometabolic risk factors related to body composition, blood pressure, glucose, and lipid levels in adulthood. We applied a multi-method intergenerational Mendelian randomization (MR) framework, combining two-sample MR (outcome GWAS, n = up to 564,160) and one-sample MR analyses (n = up to 17,484 genotyped mother-father-offspring trios with offspring cardiometabolic risk factors) from the HUNT cohort, Norway, and the UK Biobank and ALSPAC cohorts in the United Kingdom. Smoking behaviour was instrumented using genome-wide significant variants for smoking initiation and heaviness from large genome-wide association studies (2019 and 2022), with additional analyses of the CHRNA5 variant rs16969968.Results Using the two-sample MR approach, we found an average change in adult offspring waist-hip ratio (WHR) per one standard deviation (SD) increase in maternal cigarettes smoked per day of 0.25 SD (95% CI: 0.13, 0.38; 2019 GWAS), 0.19 SD (95% CI: 0.08, 0.31; 2022 GWAS) and 0.27 SD (95% CI: 0.07, 0.47; CHRNA5 rs16969968). We also found tentative evidence of comparable effects on offspring body mass index and C-reactive protein. One-sample MR analyses using CHRNA5 rs16969968, restricted to maternal ever-smokers, provided supporting evidence consistent with the primary findings for maternal smoking heaviness on offspring WHR. We found little evidence that maternal smoking initiation affected WHR, and little evidence that maternal smoking heaviness affected the remaining cardiometabolic risk factors; paternal smoking showed no clear effect on any outcome. Results from sensitivity analyses were consistent with these main findings.Conclusions Adult offspring of mothers with a propensity to heavier smoking exhibited greater central adiposity, a phenotype associated with increased cardiometabolic risk. These findings are consistent with a causal influence of maternal smoking heaviness across the preconception, perinatal, and postnatal periods on later-life offspring body fat distribution. Further triangulation using alternative causal approaches is warranted.
SN - 1741-7015
ER -