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1. Association between household cleaning product profiles evaluated by the Ménag'Score® index and asthma symptoms among women from the SEPAGES Cohort

Author

Lemire, Pierre, Chevallier, Emmanuel, Lyon-Caen, Sarah, Sévin, Etienne, Boudier, Anne, Pacheco Da Silva, Emilie, De Thuin, Christian, Slama, Rémy, Dumas, Orianne, Siroux, Valérie, Le Moual, Nicole, Eyriey, E., Licinia, A., Vellement, A., Pin, I., Hoffmann, P., Hullo, E., Llerena, C., Morin, X., Morlot, A., Lepeule, J., Lyon-Caen, S., Philippat, C., Quentin, J., Siroux, V., Slama, R., Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, National Institute for Consumption/Institut national de la consommation [Paris] (INC), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), EpiConcept [Paris], This work was supported by the European Research Council under Grant N°311765-E-DOHaD, the European Community’s Seventh Framework Programme under Grant FP7/2007-206—N°308333-892 HELIX, the European Union’s Horizon 2020 research and innovation programme under Grants N° 874583 ATHLETE Project and N°825712 OBERON Project, the French Research Agency—ANR under Grants PAPER project ANR-12-PDOC-0029-01, SHALCOH project ANR-14-CE21-0007, ANR-15-IDEX-02 and ANR-15-IDEX5, GUMME project ANR-18-CE36-005 and ETAPE project ANR—EDeN project ANR -19-CE36-0003-01, the French Agency for Food, Environmental and Occupational Health & Safety—ANSES under Grants CNAP project EST-2016-121, PENDORE project EST-2016-121 and HyPAxE project EST-2019/1/039, the Plan Cancer under (Canc’Air project), the French Cancer Research Foundation Association de Recherche sur le Cancer—ARC, the French Endowment Fund AGIR for chronic diseases—APMC under Grants projects PRENAPAR and LCI-FOT, the French Endowment Fund for Respiratory Health, the French Fund—Fondation de France under Grants CLIMATHES—00081169 and SEPAGES 5—00099903, COBANET-Sepages project was supported by Anses and Ademe under Grants COBANET: Anses-PNR-EST-2015-1-022/Ademe-1594C0091and CRESPI: Anses-PNR-EST-2017-1-101/Ademe-1762C0021/ARS Ile de France 2018–2019: Pierre Lemire benefited from a PhD scholarship of the University of Paris-Sud/Paris-Saclay, France., SEPAGES Study Group: E Eyriey, A Licinia, A Vellement, I Pin, P Hoffmann, E Hullo, C Llerena, X Morin, A Morlot, J Lepeule, S Lyon-Caen, C Philippat, I Pin, J Quentin, V Siroux, R Slama., ANR-12-PDOC-0029,PAPER,Grossesse, pollution atmospherique, epigenetique, et sante respiratoire(2012), ANR-14-CE21-0007,SHALCOH,Expositions prénatales aux phénols et santé de l'enfant : analyse longitudinale(2014), ANR-11-RARE-0002,EDEN(2011), ANR-19-CE36-0003,EDeN,Exposition précoces aux perturbateurs endocriniens et neurodéveloppement de l'enfant : le rôle de l'axe hypothalamo-hypophysaire(2019), Faraldo, Beatrice, Retour Post-Doctorant - Grossesse, pollution atmospherique, epigenetique, et sante respiratoire - - PAPER2012 - ANR-12-PDOC-0029 - PDOC - VALID, Appel à projets générique - Expositions prénatales aux phénols et santé de l'enfant : analyse longitudinale - - SHALCOH2014 - ANR-14-CE21-0007 - Appel à projets générique - VALID, ERA RARE - - EDEN2011 - ANR-11-RARE-0002 - ERA RARE - VALID, and Exposition précoces aux perturbateurs endocriniens et neurodéveloppement de l'enfant : le rôle de l'axe hypothalamo-hypophysaire - - EDeN2019 - ANR-19-CE36-0003 - AAPG2019 - VALID

Subjects
Public health, household cleaning products, Epidemiology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Public Health, Environmental and Occupational Health, Ménag'score, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, asthma
Abstract

International audience; Objective Considering household disinfectants and cleaning products (HDCP) as mixture of ingredients, rather than each ingredient individually, might help in characterizing their role in asthma. We investigated the association between HDCP and asthma, using the recently developed Ménag'Score®, a health risk assessment score based on exhaustive ingredient lists of HDCP. Methods The study is based on 103 female volunteers of the SEPAGES cohort (2014-2019), with repeated data (up to 3 collection times, 200 observations). HDCP use was assessed from a barcode-based smartphone application linked with an ingredient database. The Ménag'score® risks for health and environment were computed for each weekly used HDCP from their exhaustive ingredient data (from A: no known risk to E: highest risk). The association between the use of HDCP with a poor Ménag'score® (D or E; overall, health, environment scores) and asthma symptoms, was estimated by generalized estimating equations models adjusted for age, BMI and smoking status. Results Participants were on average 33 years old, 11% smoked and 20% had at least one asthma symptom. The Ménag'score® was computed for 540 HDCP scanned by participants. Weekly use of HDCP with a poor Ménag'score®-health (around 60% of the participants) was associated with a higher risk of asthma symptoms (OR=3.13, 95%CI:[1.32-7.43]). No association was observed for the Ménag'score®-environment. Conclusion The use of HDCP with a poor Ménag'score®-health was associated with asthma symptoms. The results support the use of the Ménag'score®-health to further evaluate the health risks of HDCP in observational studies and as a potential public health tool.

Published
2022

2. Association between household cleaning product profiles evaluated by the Ménag'Score® index and asthma symptoms among women from the SEPAGES cohort.

Author

Lemire, Pierre, Chevallier, Emmanuel, Lyon-Caen, Sarah, Sévin, Etienne, Boudier, Anne, Pacheco Da Silva, Emilie, De Thuin, Christian, Slama, Rémy, Dumas, Orianne, Siroux, Valérie, Le Moual, Nicole, The SEPAGES Study Group, Eyriey, E., Licinia, A., Vellement, A., Pin, I., Hoffmann, P., Hullo, E., Llerena, C., and Morin, X.

Subjects
CLEANING compounds, HOME furnishings, HEALTH risk assessment, ASTHMA, DISEASE risk factors, HOUSEKEEPING
Abstract

Objective: Considering household disinfectants and cleaning products (HDCP) as mixture of ingredients, rather than each ingredient individually, might help in characterizing their role in asthma. We investigated the association between HDCP and asthma, using the recently developed Ménag'Score®, a health risk assessment score based on exhaustive ingredient lists of HDCP. Methods: The study is based on 103 female volunteers of the SEPAGES cohort (2014–2019), with repeated data (up to 3 collection times, 200 observations). HDCP use was assessed from a barcode-based smartphone application linked with an ingredient database. The Ménag'score® risks for health and environment were computed for each weekly used HDCP from their exhaustive ingredient data (from A: no known risk to E: highest risk). The association between the use of HDCP with a poor Ménag'score® (D or E; overall, health, environment scores) and asthma symptoms, was estimated by generalized estimating equations models adjusted for age, BMI and smoking status. Results: Participants were on average 33 years old, 11% smoked and 20% had at least one asthma symptom. The Ménag'score® was computed for 540 HDCP scanned by participants. Weekly use of HDCP with a poor Ménag'score®-health (around 60% of the participants) was associated with a higher risk of asthma symptoms (OR 3.13, 95% CI [1.32–7.43]). No association was observed for the Ménag'score®-environment. Conclusion: The use of HDCP with a poor Ménag'score®-health was associated with asthma symptoms. The results support the use of the Ménag'score®-health to further evaluate the health risks of HDCP in observational studies and as a potential public health tool. [ABSTRACT FROM AUTHOR]

Published
2022
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3. Comparison of a Barcode-Based Smartphone Application to a Questionnaire to Assess the Use of Cleaning Products at Home and Their Association with Asthma Symptoms

Author

Lemire, Pierre, Temam, Sofia, Quinot, Catherine, Sévin, Etienne, Remacle, Sophie, Supernant, Karine, Dumas, Orianne, Le Moual, Nicole, Eyriey, E., Licinia, A., Vellement, A., Pin, Isabelle, Hofmann, P., Hullo, Églantine, Llerena, Catherine, Morin, X., Morlot, A., Lepeule, Johanna, Lyon-Caen, Sarah, Philippat, Claire, Quentin, Joane, Siroux, Valérie, Slama, Rémy, Faraldo, Beatrice, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, MGEN Foundation for Public Health [Paris] (FESP-MGEN), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), EpiConcept [Paris], The Sepages Study Group., Fondation d’entreprise MGEN pour la santé publique (FESP MGEN), Anses-PNR-EST-2015-1-022/Ademe-1594C0091, Anses-PNR-EST-2017-1-101/Ademe-1762C0021 Seventh Framework Programme, FP7: FP7/2007-206, N308333-HELIX European Research Council, ERC: N 311765-E-DOHaD Agence Nationale de la Recherche, ANR: 14-CE21-0007-01, 19-CE36-0003-01, ANR 18-CE36-005, ANR-12-PDOC-0029-01, ANR-15-IDEX, ANR-15-IDEX-02 Institut National de la Santé et de la Recherche Médicale, Inserm Fondation de France: CLI-MATHES—00081169 Commissariat Général à l'Investissement, CGI Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail, ANSES: PNR-EST-2018-1-264 Agir pour les Maladies Chroniques, Acknowledgments: We acknowledge the role of SEPAGES cohort study group: E. Eyriey, A. Licinia, A. Vellement (Groupe Hospitalier Mutualiste, Grenoble), I. Pin, P. Hofmann, E. Hullo, C. Llerena (Grenoble University Hospital, La Tronche), X. Morin (Clinique des Cèdres, Echirolles), A. Morlot (Clinique Belledonne, Saint-Martin d’Hères), J. Lepeule, S. Lyon-Caen, C. Philippat, I. Pin, J. Quentin, V. Siroux, R. Slama (Inserm, CNRS, University Grenoble Alpes IAB research center). We thank A. Benlakhryfa, L. Borges, Y. Gioria, clinical research assistants, J. Giraud, M. Marceau, M.-P. Martin, nurses, E. Charvet, A. Putod, midwives, M. Graca, K. Gridel, C. Pelini, fieldworkers, K. Guichardet, A. Levanic, C. Martel, E. Quinteiro neuropsychologists, the sta↵ from Grenoble Center for Clinical Investigation (CIC): J.-L. Cracowski, C. Cracowski, E. Hodaj, D. Abry, N. Gonnet and A. Tournier. A warm thank you also to M. Althuser, S. Althuser, F. Camus-Chauvet, P. Dusonchet, S. Dusonchet, L. Emery, P. Fabbrizio, P. Ho↵mann, D. Marchal André, X. Morin, E. Opoix, L. Pacteau, P. Rivoire, A. Royannais, C. Tomasella, T. Tomasella, D. Tournadre, P. Viossat, E. Volpi, S. Rey, E. Warembourg and clinicians from Grenoble University Hospital for their support in the recruitment of the study volunteers. We also thank A. Buchet, S.F. Caraby, J.-N. Canonica, J. Dujourdil, E. Eyriey, P. Hofmann, M. Jeannin, A. Licina, X. Morin, A. Nicolas, and all midwives from the four maternity wards of Grenoble urban areas. We thank B. Chevolon, C. Cornes, A.S. Gauchez, D. Guergour, P. Faure, J. Arnaud for thyroid hormones assessment. We thank the team of L. Chaperod (EFS) for its implication on the immunological aspects of the project. We thank G. Uzu (IRD) and J.-L. Ja↵rezo (CNRS) for their implication on PM oxidative potential assessment. We thank F.-X. Leupert, O. Bonnet and L. Goirand for the access to the birth certificate database from the Conseil Général de l’Isère. Sépages biospecimens are stored at Grenoble University Hospital (CHU-GA) biobank (bb-0033-00069), we would like to thank the whole CRB team, led by P. Mossuz and P. Lorimier, and in particular the technicians for the huge work of biospecimens processing and pooling: W. Jayar and L. Than, as well as G. Schummer. The Internet platform for secured data collection was developed by Epiconcept Paris (E. Sevin, S. Ployart, A. Polaert). SEPAGES data are stored thanks to Inserm RE-CO-NAI platform funded by Commissariat Général à l’Investissement, with the implication of Sophie de Visme (Inserm DSI). Many thanks to M.A. Charles, RE-CO-NAI coordinator, for her support. Finally, and importantly, we would like to express our sincere thanks to participants of the SEPAGES study. The authors are grateful for the help received from Ines Taarit and Mathias Clément to update the cleaning products ingredients database., Funding: The cohort was supported by the European Research Council (consolidator grant N 311765-E-DOHaD, PI, R. Slama), by the European Community’s Seventh Framework Programme (FP7/2007-206, grant N308333-HELIX, PI, M. Vrijheid), by ANR, the French Research Agency (PAPER project ANR-12-PDOC-0029-01, PI, J. Lepeule, SHALCOH project, 14-CE21-0007-01, PI, R. Slama, GUMME project, PI, R. Slama, ETAPE ANR 18-CE36-005, PI, J. Lepeule, EDeN project 19-CE36-0003-01, SYMER project, ANR-15-IDEX-02, PI, U. Schlattner, Mobil’Air project, ANR-15-IDEX, PI, S. Mathy, supported by University Grenoble-3Alpes), by ANSES (CNAP and HYPAXE projects, PI C. Philippat, PENDORE project, PNR-EST-2018-1-264, PI, V. Siroux), by Plan Cancer (Canc’Air project, PI, P. Guénel), by Association de Recherche sur le Cancer (ARC, PI, P. Guénel), by AGIR pour les maladies chroniques (PI, R. Slama and PRENAPAR project, V. Siroux), and Fonds de Recherche pour la Santé Respiratoire (FRSR, PI, I. Pin) and by Fondation de France (CLI-MATHES—00081169, J. Lepeule). We acknowledge the support of ANSES, Inserm and AGIR pour les maladies chroniques, for SEPAGES feasibility study. The support of 'SCUSI 2017' Région Auvergne-Rhône-Alpes programme is also acknowledged. COBANET-Sepages project was support by Anses and Ademe (COBANET: Anses-PNR-EST-2015-1-022/Ademe-1594C0091, PI: N Le Moual, CRESPINET: Anses-PNR-EST-2017-1-101/Ademe-1762C0021, PI: N Le Moual). Pierre Lemire benefited from a PhD scholarship of the University of Paris-Sud/Paris-Saclay, France., The cohort was supported by the European Research Council (consolidator grant N 311765-E-DOHaD, PI, R. Slama), by the European Community?s Seventh Framework Programme (FP7/2007-206, grant N308333-HELIX, PI, M. Vrijheid), by ANR, the French Research Agency (PAPER project ANR-12-PDOC-0029-01, PI, J. Lepeule, and EDeN project 19-CE36-0003-01, SYMER project, ANR-15-IDEX-02, PI, U. Schlattner, Mobil?Air project, ANR-15-IDEX, PI, S. Mathy, supported by University Grenoble-3Alpes), by ANSES (CNAP and HYPAXE projects, PI C. Philippat, PENDORE project, PNR-EST-2018-1-264, PI, V. Siroux), by Plan Cancer (Canc?Air project, PI, P. Gu?nel), by Association de Recherche sur le Cancer (ARC, PI, P. Gu?nel), by AGIR pour les maladies chroniques (PI, R. Slama and PRENAPAR project, V. Siroux), and Fonds de Recherche pour la Sant? Respiratoire (FRSR, PI, I. Pin) and by Fondation de France (CLIMATHES?00081169, J. Lepeule). We acknowledge the support of ANSES, Inserm and AGIR pour les maladies chroniques, for SEPAGES feasibility study. The support of ?SCUSI 2017? R?gion Auvergne-Rh?ne-Alpes programme is also acknowledged. COBANET-Sepages project was support by Anses and Ademe (COBANET: Anses-PNR-EST-2015-1-022/Ademe-1594C0091, PI: N Le Moual

Subjects
medicine.medical_specialty, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], lcsh:Medicine, Smartphone application, Logistic regression, Article, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Environmental health, Epidemiology, Odds Ratio, medicine, Humans, 030212 general & internal medicine, Association (psychology), smartphone application, Asthma, household cleaning products, business.industry, lcsh:R, Public Health, Environmental and Occupational Health, Asthma symptoms, Odds ratio, asthma, medicine.disease, 3. Good health, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Smartphone, business, Kappa, Disinfectants
Abstract

International audience; Household disinfectant and cleaning products (HDCPs) assessment is challenging in epidemiological research. We hypothesized that a newly-developed smartphone application was more objective than questionnaires in assessing HDCPs. Therefore, we aimed to compare both methods, in terms of exposure assessments and respiratory health effects estimates. The women of the SEPAGES birth cohort completed repeated validated questionnaires on HDCPs and respiratory health and used an application to report HDCPs and scan products barcodes, subsequently linked with an ingredients database. Agreements between the two methods were assessed by Kappa coefficients. Logistic regression models estimated associations of HDCP with asthma symptom score. The 101 participants (18 with asthma symptom score ≥1) scanned 617 different products (580 with available ingredients list). Slight to fair agreements for sprays, bleach and scented HDCP were observed (Kappa: 0.35, 0.25, 0.11, respectively). Strength of the associations between HDCP and asthma symptom score varied between both methods but all odds ratios (OR) were greater than one. The number of scanned products used weekly was significantly associated with the asthma symptom score (adjusted-OR [CI 95%]: 1.15 [1.00–1.32]). This study shows the importance of using novel tools in epidemiological research to objectively assess HDCP and therefore reduce exposure measurement errors.

Published
2021

4. Use of personal care products during pregnancy in relation to urinary concentrations of select phenols: A longitudinal analysis from the SEPAGES feasibility study

Author

Nakiwala, Dorothy, Vernet, Céline, Lyon-Caen, Sarah, Lavorel, Anna, Rolland, Matthieu, Cracowski, Claire, Pin, Isabelle, Calafat, Antonia, Slama, Rémy, Philippat, Claire, Eyriey, E., Licinia, A., Vellement, A., Hoffmann, P., Hullo, E., Llerena, C., Morin, X., Morlot, A., Lepeule, J., Quentin, J., Siroux, V., Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Service d'hospitalisation Urgences Pneumologiques - Mucoviscidose Adulte, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Philippat, Claire, and Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)

Subjects
[SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Benzophenone-3, Personal care products, Pregnant women, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, Parabens, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Bisphenols, Endocrine disruptors
Abstract

International audience; Background: Exposure to certain synthetic phenols is of growing concern, in particular among pregnant women, because of their endocrine disrupting nature. Many phenols are still authorized in personal care products (PCP). We aimed to assess if use of PCPs, by pregnant women could influence their urinary concentrations of synthetic phenols.Methods: We used a panel design with intense urine sample collection. Eight women completed a diary with exact time and use of PCPs in three weeks. We measured the concentrations of phenols (four parabens, bisphenol A and S, two dichlorophenols, triclosan, and benzophenone-3) in 178 urine samples, collected during 7 consecutive days at 3 time points during pregnancy. We characterized PCP use as the total number of PCP applications or as a single PCP use (yes/no) in three time windows (0–6, 6 to 12 and 12 to 24h before each urine sample collection). We used adjusted linear and Tobit regressions to assess associations between PCP use and phenol urinary concentrations.Results: The total number of PCP applications was positively associated with ethylparaben, propylparaben and butylparaben concentrations. We observed a peak in urinary concentration of ethylparaben, butylparaben and propylparaben at 2.86, 2.55 and 2.67 h since last PCP use, respectively and twelve different types of PCPs were positively associated with at least one of these parabens. The bisphenol S concentration increased by 12.4% (95%CI: confidence interval: 5.9; 19.3) for each additional PCP application in the 12 to 24 time window and use of specific PCPs such as anti-stretchmarks cream, facial cleanser and shower gel. Associations varied by time window.Conclusion: Our study showed that PCP use was associated with a short-term increase in the urinary concentration of ethylparaben, butylparaben and propylparaben, but not methylparaben. This study also reported a positive association between the use of PCPs and the bisphenol S concentration, a finding that warrants further investigation in cohorts with repeated collection of urine samples and detailed information on PCP use.

Published
2020

5. Using methylome data to inform exposome-health association studies: An application to the identification of environmental drivers of child body mass index

Author

Nakiwala, Dorothy, Vernet, Céline, Lavorel, Anna, Cracowski, Claire, Calafat, Antonia, Eyriey, E., Licinia, A., Vellement, A., Hoffmann, P., Hullo, E., Llerena, C., Morin, X., Morlot, A., Lepeule, J., Quentin, J., Siroux, V., Rolland, Matthieu, Lyon-Caen, Sarah, Sakhi, Amrit, Pin, Isabelle, Sabaredzovic, Azemira, Thomsen, Cathrine, Philippat, Claire, Cadiou, Solène, Bustamante, Mariona, Agier, Lydiane, Andrusaityte, Sandra, Basagaña, Xavier, Carracedo, Angel, Chatzi, Leda, Grazuleviciene, Regina, Gonzalez, Juan, Gutzkow, Kristine, MAITRE, Léa, Mason, Dan, Millot, Frédéric, Nieuwenhuijsen, Mark, Papadopoulou, Eleni, Santorelli, Gillian, Saulnier, Pierre-Jean, Vives, Marta, Wright, John, Vrijheid, Martine, Slama, Rémy, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Grenoble Alpes (UGA), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), European Project, U823, IAB Research Center, Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Department of Environmental Sciences, Vytautas Magnus University, Kaunas, Lithuania, Fundación Pública Galega Medicina Xenómica - SERGAS [Santiago de Compostela, Spain] (Grupo de Medicina Xenómica), CIBER de Enfermedades Raras (CIBERER)-Universidade de Santiago de Compostela [Spain] (USC ), Norwegian Institute of Public Health [Oslo, Norway] (NIPH), Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK (BIHR), CIBER Epidemiologia y Salud Pùblica [Madrid, Spain] (CIBERESP), and Instituto de Salud Carlos III [Madrid] (ISC)

Subjects
Reverse causality, dimension reduction – DNA methylation, 010504 meteorology & atmospheric sciences, [SDV]Life Sciences [q-bio], MESH: Epigenome, Bisphenols, 010501 environmental sciences, MESH: Triclosan, Bioinformatics, 01 natural sciences, Body Mass Index, Epigenome, MESH: Pregnancy, Pooled biospecimens, Benzophenone-3, Pregnancy, MESH: Child, Medicine, Child, lcsh:Environmental sciences, General Environmental Science, lcsh:GE1-350, MESH: Exposome, 2. Zero hunger, 3. Good health, Biological a priori, Exposome, MESH: Environmental Pollutants, Personal care products, [SDE]Environmental Sciences, Cohort, DNA methylation, Environmental Pollutants, Female, Infants, MESH: Environmental Exposure, Parabens, Article, MESH: Body Mass Index, Humans, Endocrine disruptors, 0105 earth and related environmental sciences, Genetic association, MESH: Humans, business.industry, Pregnant women, Environmental Exposure, Triclosan, Peripheral blood, Child body mass index – exposome, Multiple comparisons problem, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female, Body mass index
Abstract

Background: The exposome is defined as encompassing all environmental exposures one undergoes from conception onwards. Challenges of the application of this concept to environmental-health association studies include a possibly high false-positive rate. Objectives: We aimed to reduce the dimension of the exposome using information from DNA methylation as a way to more efficiently characterize the relation between exposome and child body mass index (BMI). Methods: Among 1,173 mother-child pairs from HELIX cohort, 216 exposures ("whole exposome") were characterized. BMI and DNA methylation from immune cells of peripheral blood were assessed in children at age 6-10 years. A priori reduction of the methylome to preselect BMI-relevant CpGs was performed using biological pathways. We then implemented a tailored Meet-in-the-Middle approach to identify from these CpGs candidate mediators in the exposome-BMI association, using univariate linear regression models corrected for multiple testing: this allowed to point out exposures most likely to be associated with BMI ("reduced exposome"). Associations of this reduced exposome with BMI were finally tested. The approach was compared to an agnostic exposome-wide association study (ExWAS) ignoring the methylome. Results: Among the 2284 preselected CpGs (0.6% of the assessed CpGs), 62 were associated with BMI. Four factors (3 postnatal and 1 prenatal) of the exposome were associated with at least one of these CpGs, among which postnatal blood level of copper and PFOS were directly associated with BMI, with respectively positive and negative estimated effects. The agnostic ExWAS identified 18 additional postnatal exposures, including many persistent pollutants, generally unexpectedly associated with decreased BMI. Discussion: Our approach incorporating a priori information identified fewer significant associations than an agnostic approach. We hypothesize that this smaller number corresponds to a higher specificity (and possibly lower sensitivity), compared to the agnostic approach. Indeed, the latter cannot distinguish causal relations from reverse causation, e.g. for persistent compounds stored in fat, whose circulating level is influenced by BMI. The study has received funding from the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement n° 308,333 – the HELIX project for data collection and analyses. The Norwegian Mother and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, NIH/NIEHS (contract no N01-ES-75558), NIH/NINDS (grant n°0.1 UO1 NS 047537–01 and grant no.2 UO1 NS 047537-06A1). We also received support from Région Auvergne-Rhône-Alpes for collaborations with Catalunya. Dr. Chatzi was supported by NIH P30ES007048, R21ES029681, R01ES029944, R01ES030364, R21ES028903, and by Environmental Protection Agency RD-83544101.

Published
2020

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