Study of the combined effect of maternal tobacco smoking and polygenic risk scores on birth weight and body mass index in childhood

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• dc.contributor.author Fuentes Páez, Georgina
• dc.contributor.author Aguilar Lacasaña, Sofía
• dc.contributor.author Casas Sanahuja, Maribel
• dc.contributor.author Maitre, Léa
• dc.contributor.author Ruiz Arenas, Carlos, 1990-
• dc.contributor.author Sunyer Deu, Jordi
• dc.contributor.author Urquiza, José M.
• dc.contributor.author Vrijheid, Martine
• dc.contributor.author Vilor Tejedor, Natàlia, 1988-
• dc.contributor.author Bustamante Pineda, Mariona
• dc.date.accessioned 2022-10-28T06:49:58Z
• dc.date.available 2022-10-28T06:49:58Z
• dc.date.issued 2022
• dc.description.abstract Background: Maternal smoking during pregnancy has adverse health effects on the offspring, including lower birth weight and increased risk for obesity. These outcomes are also influenced by common genetic polymorphisms. We aimed to investigate the combined effect of maternal smoking during pregnancy and genetic predisposition on birth weight and body mass index (BMI)-related traits in 1,086 children of the Human Early Life Exposome (HELIX) project. Methods: Maternal smoking during pregnancy was self-reported. Phenotypic traits were assessed at birth or at the age of 8 years. Ten polygenic risk scores (PRSs) per trait were calculated using the PRSice v2 program. For birth weight, we estimated two sets of PRSs based on two different base GWAS summary statistics: PRS-EGG, which includes HELIX children, and PRS-PanUK, which is completely independent. The best PRS per trait (highest R 2) was selected for downstream analyses, and it was treated in continuous or categorized into three groups. Multivariate linear regression models were applied to evaluate the association of the explanatory variables with the traits of interest. The combined effect was evaluated by including an interaction term in the regression models and then running models stratified by the PRS group. Results: BMI-related traits were correlated among them but not with birth weight. A similar pattern was observed for their PRSs. On average, the PRSs explained ∼4% of the phenotypic variation, with higher PRS values related to higher trait values (p-value <5.55E-08). Sustained maternal smoking was associated with lower birth weight and higher BMI and related traits (p-value <2.99E-02). We identified a gene by environment (GxE) interaction for birth weight between sustained maternal smoking and the PRS-EGG in three groups (p-value interaction = 0.01), which was not replicated with the PRS-PanUK (p-value interaction = 0.341). Finally, we did not find any statistically significant GxE interaction for BMI-related traits (p-value interaction >0.237). Conclusion: Sustained maternal smoking and the PRSs were independently associated with birth weight and childhood BMI-related traits. There was low evidence of GxE interactions.
• dc.description.sponsorship The study has received funding from the European Community’s Seventh Framework Programme (FP7/2007–206) under the grant agreement no 308333 (HELIX project) and the H2020-EU.3.1.2. - Preventing Disease Programme under grant agreement no 874583 (ATHLETE project). Genotyping was supported by the projects PI17/01225 and PI17/01935, funded by the Instituto de Salud Carlos III and co-funded by European Union (ERDF, “A way to make Europe”) and the Centro Nacional de Genotipado-CEGEN (PRB2-ISCIII). NV-T is funded by a postdoctoral grant, Juan de la Cierva Programme (FJC 2018–038085-I), Ministry of Science and Innovation–Spanish State Research Agency. NV-T research is also supported by the “la Caixa'' Foundation (LCF/PR/GN17/10300004) and the Health Department of the Catalan Government (Health Research and Innovation Strategic Plan (PERIS) 2016–2020 grant #SLT002/16/00201). LM is funded by a Juan de la Cierva-Incorporación fellowship (IJC 2018–035394-I) awarded by the Spanish Ministerio de Economía, Industria y Competitividad. M-AC holds a Miguel Servet fellowship (MS16/00128) funded by Instituto de Salud Carlos III and co-funded by European Social Fund “Investing in your future”. JU is granted by the Spanish regional program PERIS (Ref: SLT017/20/000119) Granted by Departament de Salut de la Generalitat de Catalunya. BiB received core infrastructure funding from the Wellcome Trust (WT101597MA) and a joint grant from the UK Medical Research Council (MRC) and Economic and Social Science Research Council (ESRC) (MR/N024397/1) and the National Institute for Health Research Applied Research Collaboration Yorkshire and Humber (NIHR200166). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. INMA data collections were supported by grants from the Instituto de Salud Carlos III, CIBERESP, and the Generalitat de Catalunya-CIRIT. KANC was funded by the grant of the Lithuanian Agency for Science Innovation and Technology (6-04-2014_31V-66). The Norwegian Mother, Father and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research. The Rhea project was financially supported by European projects (EU FP6-2003-Food-3-NewGeneris, EU FP6. STREP Hiwate, EU FP7 ENV. 2007.1.2.2.2. Project No 211250 Escape, EU FP7-2008-ENV-1.2.1.4 EnviroGenomarkers, EU FP7-HEALTH-2009- single-stage CHICOS, EU FP7 ENV. 2008.1.2.1.6. Proposal No 226285 ENRIECO, EU- FP7- HEALTH-2012 Proposal No 308333 HELIX), and the Greek Ministry of Health (Program of Prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece: 2011–2014; “Rhea Plus”: Primary Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012–15). ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX 2018-000806-S) and support from the Generalitat de Catalunya through the CERCA Program. RG acknowledge the support of the Spanish Ministry of Science, Innovation, and Universities to the EMBL partnership, the Centro de Excelencia Severo Ochoa, and the CERCA Programme/Generalitat de Catalunya.
• dc.format.mimetype application/pdf
• dc.identifier.citation Fuentes-Paez G, Escaramís G, Aguilar-Lacasaña S, Andrusaityte S, Brantsæter AL, Casas M et al. Study of the combined effect of maternal tobacco smoking and polygenic risk scores on birth weight and body mass index in childhood. Front Genet. 2022 May 12;13:867611. DOI: 10.3389/fgene.2022.867611
• dc.identifier.doi http://dx.doi.org/10.3389/fgene.2022.867611
• dc.identifier.issn 1664-8021
• dc.identifier.uri http://hdl.handle.net/10230/54632
• dc.language.iso eng
• dc.publisher Frontiers
• dc.relation.ispartof Front Genet. 2022 May 12;13:867611
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/308333
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/874583
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/211250
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/226285
• dc.rights © 2022 Fuentes-Paez, Escaramís, Aguilar-Lacasaña, Andrusaityte, Brantsæter, Casas, Charles, Chatzi, Lepeule, Grazuleviciene, Gützkow, Heude, Maitre, Ruiz-Arenas, Sunyer, Urquiza, Yang, Wright, Vrijheid, Vilor-Tejedor and Bustamante. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Birth weight
• dc.subject.keyword Body mass index
• dc.subject.keyword Children
• dc.subject.keyword Fat mass
• dc.subject.keyword Gene by environment (GxE) interaction
• dc.subject.keyword Maternal smoking
• dc.subject.keyword Polygenic risk score
• dc.subject.keyword Waist circumference
• dc.title Study of the combined effect of maternal tobacco smoking and polygenic risk scores on birth weight and body mass index in childhood
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion