ArticleInternational journal of epidemiology2020
Proxy gene-by-environment Mendelian randomization study confirms a causal effect of maternal smoking on offspring birthweight, but little evidence of long-term influences on offspring health.
Article in International journal of epidemiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 4 of them syntheses that pooled it.
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Who cites it
22 citing papers in PubMed, 4 syntheses or guidelines pooled it, 44 citations in OpenAlex.
- Assessing the causal effects of environmental tobacco smoke exposure: a meta-analytic Mendelian randomization study.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2026Pooled it
- Large-scale GWAS of strabismus identifies risk loci and provides support for a link with maternal smoking.Nature communications · 2025Pooled it
- Methodological approaches, challenges, and opportunities in the application of Mendelian randomisation to lifecourse epidemiology: A systematic literature review.European journal of epidemiology · 2024Pooled it
- Smoking during pregnancy and its effect on placental weight: a Mendelian randomization study.BMC pregnancy and childbirth · 2024Pooled it
- Smoking during pregnancy is associated with child overweight independent of maternal pre-pregnancy BMI and genetic predisposition to adiposity.Scientific reports · 2022Trial
- Exploring parental prenatal influences on child health: A multicohort study and data visualisation tool.PLoS medicine · 2026Article
- Extending the Use of Mendelian Randomisation With Non-Inherited Variants to Assess Socially Transmitted Parental Exposures Under Assortative Mating.Genetic epidemiology · 2026Article
- A structural mean modeling Mendelian randomization approach to investigate the lifecourse effect of adiposity: applied and methodological considerations.American journal of epidemiology · 2026Article
- Investigating the Relationship Between Maternal Smoking During Pregnancy and Offspring Handedness: Extending the Proxy Gene-by-Environment Mendelian Randomization Study Design to Include Polygenic Risk Scores.Behavior genetics · 2025Article
- Woolf et al's "GWAS by subtraction" is not useful for cross-generational Mendelian randomization studies.BMC research notes · 2025Article
- Associations of Maternal Smoking During Pregnancy and Genetic Susceptibility with Incident Asthma from a Cohort Study.Prevention science : the official journal of the Society for Prevention Research · 2025Article
- Article
- Prenatal maternal stress: triangulating evidence for intrauterine exposure effects on birth and early childhood outcomes across multiple approaches.BMC medicine · 2025Article
- Dietary Patterns, Food Intake and Health: New Evidence from Epidemiological and Genetic Studies.Nutrients · 2024Article
- Perinatal exposures and adolescence overweight: The role of shared maternal-offspring pathways.Atherosclerosis · 2024Article
- Proxy gene-by-environment Mendelian randomization study of the association between cigarette smoking during pregnancy and offspring mental health.International journal of epidemiology · 2023Article
- Deriving GWAS summary estimates for paternal smoking in UK biobank: a GWAS by subtraction.BMC research notes · 2023Article
- Exploring and mitigating potential bias when genetic instrumental variables are associated with multiple non-exposure traits in Mendelian randomization.European journal of epidemiology · 2022Article
- The Interplay between Maternal Smoking and Genes in Offspring Birth Weight.medRxiv : the preprint server for health sciences · 2020Article
- Estimating indirect parental genetic effects on offspring phenotypes using virtual parental genotypes derived from sibling and half sibling pairs.PLoS genetics · 2020Article
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3 authors at 1 institution in 1 country.
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Abstract
backgroundA lack of genetic data across generations makes transgenerational Mendelian randomization (MR) difficult. We used UK Biobank and a novel proxy gene-by-environment MR to investigate effects of maternal smoking heaviness in pregnancy on offspring health, using participants' (generation one: G1) genotype (rs16969968 in CHRNA5) as a proxy for their mothers' (G0) genotype.
methodsWe validated this approach by replicating an established effect of maternal smoking heaviness on offspring birthweight. Then we applied this approach to explore effects of maternal (G0) smoking heaviness on offspring (G1) later life outcomes and on birthweight of G1 women's children (G2).
resultsEach additional smoking-increasing allele in offspring (G1) was associated with a 0.018 [95% confidence interval (CI): -0.026, -0.009] kg lower G1 birthweight in maternal (G0) smoking stratum, but no meaningful effect (-0.002 kg; 95% CI: -0.008, 0.003) in maternal non-smoking stratum (interaction P-value = 0.004). The differences in associations of rs16969968 with grandchild's (G2) birthweight between grandmothers (G0) who did, versus did not, smoke were heterogeneous (interaction P-value = 0.042) among mothers (G1) who did (-0.020 kg/allele; 95% CI: -0.044, 0.003), versus did not (0.007 kg/allele; 95% CI: -0.005, 0.020), smoke in pregnancy.
conclusionsOur study demonstrated how offspring genotype can be used to proxy for the mother's genotype in gene-by-environment MR. We confirmed the causal effect of maternal (G0) smoking on offspring (G1) birthweight, but found little evidence of an effect on G1 longer-term health outcomes. For grandchild's (G2) birthweight, the effect of grandmother's (G0) smoking heaviness in pregnancy may be modulated by maternal (G1) smoking status in pregnancy.
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