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Isabelle Pin, Isa Cerveri, Lucia Cazzoletti, Andrei Malinovschi, Josep M. Antó, Simone Accordini, Deborah Jarvis, David Gislason, Ane Johannessen, Bénédicte Leynaert, Pierpaolo Marchetti, Diogenes S. Ferreira, Nicole Probst-Hensch, Alessandro Marcon, Christer Janson, Rain Jögi, Judith Garcia-Aymerich, Angelo Corsico, Joachim Heinrich, Joost Weyler, Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 2610, 4350 97/0035-01, 99/0034-01, 99/0034-02 97/0035, 97/0035-02, 99/0034-04, 99/0034-06, 99/0034-07, 99/350 90MR/10, 91AF/6 SEPAR R01 HL62633-01 018996 911631 Russell Sage Foundation, RSF ResMed Foundation AstraZeneca GlaxoSmithKline, GSK Novartis U.S. Public Health Service, USPHS: R01 HL62633-01 Chiesi Farmaceutici, Chiesi Faculty of Arts and Sciences, Harvard University, FAS Boehringer Ingelheim VÃ¥rdalstiftelsen Freiwillige Akademische Gesellschaft, FAG Commercial Aircraft of China, COMAC Wellcome Trust, WT: WT 084703MA Horizon 2020 Framework Programme, H2020: 633212 Growing Spine Foundation, GSF Gobierno del Principado de Asturias Blond McIndoe Research Foundation, BMRF Asthma and Allergy Foundation of America, AAFA Ministerio de Sanidad, Consumo y Bienestar Social, MISAN Union Chimique Belge, UCB Medical Research Council, MRC: 92091, G0901214 National Institute for Health Research, NIHR British Lung Foundation, BLF European Commission, EC: EU-PEAL PL01237 National Health and Medical Research Council, NHMRC: G.0402.00 Asthma Foundation of Victoria Deutsche Forschungsgemeinschaft, DFG: FR1526/1-1, HE 3294/10-1, MA 711/4-1, MA 711/6-1, NO 262/7-1 Agence Nationale de la Recherche, ANR Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, SNSF: 3100-059302, 3200-042532, 3200-052720, 3247-065896, 3247BO-104283, 3247BO-104284, 3247BO-104288, 33CSCO-108796, 33CSCO-134276/1, 4026-028099, 4026-28099 Eesti Teadusfondi, ETF: 1088 ForskningsrÃ¥det för Arbetsliv och Socialvetenskap, FAS Eesti Teadusagentuur: 562 Bundesamt für Gesundheit, BAG Belgian Federal Science Policy Office, BELSPO Generalitat de Catalunya Consell Català de Recerca i Innovació: 1999SGR 00241 Haridus- ja Teadusministeerium: SF0180060s09 Hjärt-Lungfonden Consiglio Nazionale delle Ricerche, CNR Instituto de Salud Carlos III, ISCIII: C03/011, C03/09 Háskóli Íslands, HI Norges ForskningsrÃ¥d: 101422/310, 214123 Medicinska ForskningsrÃ¥det, MFR Cancéropôle Ile de France Russian Science Foundation, RSF: 381/05.93 Ministeriet Sundhed Forebyggelse SUVA Sociedad Española de Neumología y Cirugía Torácica, SEPAR: FIS 09/01511, FIS PS09/00716, FIS PS09/02185, FIS PS09/03190, SEPAR 1001/2010 Horizon 2020 Universiteit Antwerpen Comité des Maladies Respiratoires de l'Isère Comissió Interdepartamental de Recerca i Innovació Tecnològica, CIRIT: 1997 SGR 00079, 1999 SGR 00214 Servicio Murciano de Salud Regione del Veneto Regione Piemonte Astma- och Allergiförbundet Centre Hospitalier Universitaire de Bordeaux, CHU de Bordeaux Office Fédéral de l'Education et de la Science, OFES Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie, BMBWF Helmholtz Zentrum München Lungenliga Schweiz Ministerio de Medio Ambiente y Medio Rural y Marino, MARM: G03/176 Ministère des Solidarités et de la Santé INCLIVA Instituto de Investigación Sanitaria: 91/0016-060-05/E, 92/0319, 93/0393, PS09/00716, PS09/01511, PS09/02185, PS09/02457, PS09/03190 Fundació Autònoma Solidària, FAS Servicio Andaluz de Salud, SAS, The ALEC study is funded by the European Union's Horizon 2020 Research and Innovation programme under grant agreement number 633212. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. National funders who supported data collection in the original studies are listed in Appendix E4 in this article's Online Repository at www.jaci-inpractice.org. The funders had no role in the writing of the manuscript or the decision to submit it for publication.Conflicts of interest: D. S. Ferreira reports grants from the Asthma Foundation of Victoria, Allen and Hanburys, National Health and Medical Research Council. I. Pin reports travel grants and honoraria from Novartis, Zambon, and AstraZeneca, and nonfinancial support from AGIR?dom. R. J?gi reports grants from Estonian Research Council Personal Research (grant no. 562), and consultancy, lecture, and travel fees from GlaxoSmithKline, Boehringer, and Novartis. The rest of the authors report no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work.Financial support for ECRHS I: The coordination of this work was supported by the European Commission, and the authors and participants are grateful to the late C. Baya and M. Hallen for their help during the study and K. Vuylsteek and the members of the COMAC for their support. The following grants helped to fund the local studies: Australia: Asthma Foundation of Victoria, Allen and Hanbury's, Belgium: Belgian Science Policy Office, National Fund for Scientific Research, Estonia: Estonian Science Foundation (grant no. 1088), France: Minist?re de la Sant?, Glaxo France, Institut Pneumologique d'Aquitaine, Contrat de Plan Etat-R?gion Languedoc-Rousillon, Caisse nationale de l'assurance maladie des travailleurs salari?s, Comit? national contre les maladies respiratoires et la tuberculose (90MR/10, 91AF/6), Ministre delegu? de la sant?, R?seau national de sant? publique, France, Germany: Helmholtz Zentrum Munich and Bundesminister f?r Forschung und Technologie, Italy: Ministero dell'Universit? e della Ricerca Scientifica e Tecnologica, Consiglio Nazionale delle Ricerche, Regione Veneto (grant RSF no. 381/05.93), Norway: Norwegian Research Council project no. 101422/310, Portugal: Glaxo Farmac?utica Lda, Sandoz Portugesa, Spain: Fondo de Investigaci?n Sanitaria (nos. 91/0016-060-05/E, 92/0319, and 93/0393), Hospital General de Albacete, Hospital General Juan Ram?n Jim?nez, Direcci?n Regional de Salud P?blica (Consejer?a de Sanidad del Principado de Asturias), Consell Interdepartamental de Recerca i Innovaci? Tecnol?gica (1997 SGR 00079), and Servicio Andaluz de Salud, Sweden: The Swedish Medical Research Council, the Swedish Heart-Lung Foundation, the Swedish Association against Asthma and Allergy, Switzerland: Swiss National Science Foundation (grant no. 4026-28099), and UK: National Asthma Campaign, British Lung Foundation, Department of Health, South Thames Regional Health Authority.Financial support for ECRHS II: Australia: National Health and Medical Research Council, Belgium: Antwerp: Fund for Scientific Research (grant code G.0402.00), University of Antwerp, and Flemish Health Ministry, Estonia: Tartu: Estonian Science Foundation (grant no. 4350), France: (All) Programme Hospitalier de Recherche Clinique?Direction de la Recherche Clinique de Grenoble 2000 number 2610, Ministry of Health, Minist?re de l'Emploi et de la Solidarit?, Direction G?nerale de la Sant?, Centre Hospitalier Universitaire de Grenoble, Bordeaux: Institut Pneumologique d'Aquitaine, Grenoble: Comite des Maladies Respiratoires de l'Isere, Montpellier: Aventis (France), Direction Regionale des Affaires Sanitaires et Sociales Languedoc-Roussillon, Paris: Union Chimique Belge-Pharma (France), Aventis (France), Glaxo France, Germany: Erfurt: GSF?National Research Centre for Environment and Health, Deutsche Forschungsgemeinschaft (grant code FR1526/1-1), Hamburg: GSF?National Research Centre for Environment and Health, Deutsche Forschungsgemeinschaft (grant code MA 711/4-1), Iceland: Reykjavik: Icelandic Research Council and Icelandic University Hospital Fund, Italy: Pavia: GlaxoSmithKline Italy, Italian Ministry of University and Scientific and Technological Research (MURST), and Local University Funding for Research 1998 and 1999, Turin: Azienda Sanitaria Locale 4 Regione Piemonte (Italy), Azienda Ospedaliera Centro Traumatologico Ospedaliero/Centro Traumatologico Ortopedico?Istituto Clinico Ortopedico Regina Maria Adelaide Regione Piemonte, Verona: Ministero dell'Universit? e della Ricerca Scientifica (MURST), Glaxo Wellcome s.p.a., Norway: Bergen: Norwegian Research Council, Norwegian Asthma and Allergy Association, Glaxo Wellcome AS, and Norway Research Fund, Spain: Fondo de Investigacion Santarias (grant codes 97/0035-01, 99/0034-01, and 99/0034-02), Hospital Universitario de Albacete, Consejeria de Sanidad, Barcelona: Sociedad Espanola de Neumolog?a y Cirug?a Toracica, Public Health Service (grant code R01 HL62633-01), Fondo de Investigaciones Santarias (grant codes 97/0035-01, 99/0034-01, and 99/0034-02), Consell Interdepartamentalde Recerca i Innovaci? Tecnol?gica (grant code 1999SGR 00241), Instituto de Salud Carlos III, Red de Centros de Epidemiolog?a y Salud P?blica, C03/09, Red de Bases moleculares y fisiol?gicas de las Enfermedades Respiratorias, C03/011 and Red de Grupos Infancia y Medio Ambiente G03/176, Huelva: Fondo de Investigaciones Santarias (grant codes 97/0035-01, 99/0034-01, and 99/0034-02), Galdakao: Basque Health Department, Oviedo: Fondo de Investigaciones Sanitaria (97/0035-02, 97/0035, 99/0034-01, 99/0034-02, 99/0034-04, 99/0034-06, 99/350, and 99/0034-07), European Commission (EU-PEAL PL01237), Generalitat de Catalunya (CIRIT 1999 SGR 00214), Hospital Universitario de Albacete, Sociedad Espa?ola de Neumolog?a y Cirug?a Tor?cica (SEPAR R01 HL62633-01), Red de Centros de Epidemiolog?a y Salud P?blica (C03/09), Red de Bases moleculares y fisiol?gicas de las Enfermedades Respiratorias (C03/011), and Red de Grupos Infancia y Medio Ambiente (G03/176, 97/0035-01, 99/0034-01, and 99/0034-02), Sweden: G?teborg, Umea, AND Uppsala: Swedish Heart Lung Foundation, Swedish Foundation for Health Care Sciences and Allergy Research, Swedish Asthma and Allergy Foundation, Swedish Cancer and Allergy Foundation, and Swedish Council for Working Life and Social Research (FAS), Switzerland: Basel: Swiss National Science Foundation, Swiss Federal Office for Education and Science, and Swiss National Accident Insurance Fund, UK: Ipswich and Norwich: Asthma UK (formerly known as National Asthma Campaign).Financial support for ECRHS III: Australia: National Health and Medical Research Council, Belgium: Antwerp: South and Antwerp City: Research Foundation Flanders (grant code G.0.410.08.N.10), Estonia: Tartu: the Estonian Ministry of Education (SF0180060s09), France: (All): Minist?re de la Sant?, Programme Hospitalier de Recherche Clinique national 2010, Bordeaux: INSERM U897 Universit? Bordeaux segalen, Grenoble: Comite Scientifique AGIRadom 2011, and Paris: Agence Nationale de la Sant?, R?gion Ile de France, domaine d'int?r?t majeur, Germany: Erfurt: German Research Foundation (HE 3294/10-1), Hamburg: German Research Foundation (MA 711/6-1, NO 262/7-1), Iceland: Reykjavik: The Landspitali University Hospital Research Fund, University of Iceland Research Fund, ResMed Foundation, California, USA, Orkuveita Reykjavikur (Geothermal plant), and Vegager?in (The Icelandic Road Administration, Italy: All Italian centers were funded by the Italian Ministry of Health, Chiesi Farmaceutici SpA, in addition, Verona was funded by Cariverona Foundation and Education Ministry (Ministero dell'Istruzione, dell'Universit? e della Ricerca), Norway: Norwegian Research Council (grant no. 214123), Western Norway Regional Health Authorities (grant no. 911631), and Blond McIndoe Research Foundation, Spain: Fondo de Investigaci?n Sanitaria (PS09/02457, PS09/00716, PS09/01511, PS09/02185, PS09/03190), Servicio Andaluz de Salud, Sociedad Espa?ola de Neumolog?a y Cirurg?a Tor?cica (SEPAR 1001/2010), Fondo de Investigaci?n Sanitaria (PS09/02457), Barcelona: Fondo de Investigaci?n Sanitaria (FIS PS09/00716), Galdakao: Fondo de Investigaci?n Sanitaria (FIS 09/01511), Huelva: Fondo de Investigaci?n Sanitaria (FIS PS09/02185) and Servicio Andaluz de Salud, Oviedo: Fondo de Investigaci?n Sanitaria (FIS PS09/03190), Sweden: All centers were funded by The Swedish Heart and Lung Foundation, The Swedish Asthma and Allergy Association, The Swedish Association against Lung and Heart Disease, Swedish Research Council for health, working life and welfare, G?teborg: also received further funding from the Swedish Council for Working Life and Social Research. Umea: also received funding from Vasterbotten Country Council ALF grant, Switzerland: The Swiss National Science Foundation (grants nos. 33CSCO-134276/1, 33CSCO-108796, 3247BO-104283, 3247BO-104288, 3247BO-104284, 3247-065896, 3100-059302, 3200-052720, 3200-042532, and 4026-028099), The Federal Office for Forest, Environment and Landscape, The Federal Office of Public Health, The Federal Office of Roads and Transport, the canton's government of Aargan, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino, Valais, and Z?rich, the Swiss Lung League, the canton's Lung League of Basel-Stadt/Basel, Landschaft, Geneva, Ticino, Valais, and Zurich, SUVA, Freiwillige Akademische Gesellschaft, UBS Wealth Foundation, Talecris Biotherapeutics GmbH, Abbott Diagnostics, European Commission 018996 (GABRIEL), Wellcome Trust WT 084703MA, and UK: Medical Research Council (grant no.92091), support also provided by the National Institute for Health Research through the Primary Care Research Network., Financial support for ECRHS III: Australia: National Health and Medical Research Council, Estonia: Tartu: the Estonian Ministry of Education ( SF0180060s09 ), France: (All): Ministère de la Santé, Programme Hospitalier de Recherche Clinique national 2010, Bordeaux: INSERM U897 Université Bordeaux segalen, and Paris: Agence Nationale de la Santé, Région Ile de France, domaine d'intérêt majeur, Germany: Erfurt: German Research Foundation ( HE 3294/10-1 ), Hamburg: German Research Foundation ( MA 711/6-1 , NO 262/7-1 ), Iceland: Reykjavik: The Landspitali University Hospital Research Fund, University of Iceland Research Fund, ResMed Foundation , California, USA , Orkuveita Reykjavikur (Geothermal plant), and Vegagerðin (The Icelandic Road Administration, Italy: All Italian centers were funded by the Italian Ministry of Health , Chiesi Farmaceutici SpA, in addition, Verona was funded by Cariverona Foundation and Education Ministry (Ministero dell'Istruzione, dell'Università e della Ricerca), Norway: Norwegian Research Council (grant no. 214123 ), Western Norway Regional Health Authorities (grant no. 911631 ), and Blond McIndoe Research Foundation, Spain: Fondo de Investigación Sanitaria (PS09/02457, PS09/00716, PS09/01511, PS09/02185, PS09/03190), Servicio Andaluz de Salud, Sociedad Española de Neumología y Cirurgía Torácica ( SEPAR 1001/2010), Fondo de Investigación Sanitaria (PS09/02457), Barcelona: Fondo de Investigación Sanitaria (FIS PS09/00716), Galdakao: Fondo de Investigación Sanitaria (FIS 09/01511), Huelva: Fondo de Investigación Sanitaria (FIS PS09/02185) and Servicio Andaluz de Salud, Oviedo: Fondo de Investigación Sanitaria (FIS PS09/03190), Sweden: All centers were funded by The Swedish Heart and Lung Foundation, The Swedish Asthma and Allergy Association , The Swedish Association against Lung and Heart Disease , Swedish Research Council for health, working life and welfare, Göteborg: also received further funding from the Swedish Council for Working Life and Social Research . Umea: also received funding from Vasterbotten Country Council ALF grant, Switzerland: The Swiss National Science Foundation (grants nos. 33CSCO-134276/1 , 33CSCO-108796 , 3247BO-104283 , 3247BO-104288 , 3247BO-104284 , 3247-065896 , 3100-059302 , 3200-052720 , 3200-042532 , and 4026-028099 ), The Federal Office for Forest, Environment and Landscape, The Federal Office of Public Health, The Federal Office of Roads and Transport, the canton's government of Aargan, Basel-Stadt, Basel-Land, Geneva, Luzern, Ticino, Valais, and Zürich, the Swiss Lung League , the canton's Lung League of Basel-Stadt/Basel, Landschaft, Geneva, Ticino, Valais, and Zurich, SUVA, Freiwillige Akademische Gesellschaft , UBS Wealth Foundation, Talecris Biotherapeutics GmbH, Abbott Diagnostics , European Commission 018996 (GABRIEL), Wellcome Trust WT 084703MA, and UK: Medical Research Council (grant no. 92091 ), support also provided by the National Institute for Health Research through the Primary Care Research Network ., Conflicts of interest: D. S. Ferreira reports grants from the Asthma Foundation of Victoria , Allen and Hanburys , National Health and Medical Research Council . I. Pin reports travel grants and honoraria from Novartis , Zambon , and AstraZeneca , and nonfinancial support from AGIRàdom. R. Jõgi reports grants from Estonian Research Council Personal Research (grant no. 562 ), and consultancy, lecture, and travel fees from GlaxoSmithKline, Boehringer, and Novartis. The rest of the authors report no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years, and no other relationships or activities that could appear to have influenced the submitted work., Financial support for ECRHS II: Australia: National Health and Medical Research Council, Belgium: Antwerp: Fund for Scientific Research (grant code G.0402.00 ), University of Antwerp , and Flemish Health Ministry, Estonia: Tartu: Estonian Science Foundation (grant no. 4350 ), France: (All) Programme Hospitalier de Recherche Clinique—Direction de la Recherche Clinique de Grenoble 2000 number 2610, Ministry of Health , Ministère de l’Emploi et de la Solidarité, Direction Génerale de la Santé, Centre Hospitalier Universitaire de Grenoble, Bordeaux: Institut Pneumologique d’Aquitaine, Grenoble: Comite des Maladies Respiratoires de l’Isere, Germany: Erfurt: GSF— National Research Centre for Environment and Health , Deutsche Forschungsgemeinschaft (grant code FR1526/1-1 ), Hamburg: GSF— National Research Centre for Environment and Health , Deutsche Forschungsgemeinschaft (grant code MA 711/4-1 ), Turin: Azienda Sanitaria Locale 4 Regione Piemonte (Italy), Azienda Ospedaliera Centro Traumatologico Ospedaliero/Centro Traumatologico Ortopedico—Istituto Clinico Ortopedico Regina Maria Adelaide Regione Piemonte, Verona: Ministero dell’Università e della Ricerca Scientifica (MURST), Glaxo Wellcome s.p.a., Norway: Bergen: Norwegian Research Council , Norwegian Asthma and Allergy Association , Glaxo Wellcome AS , and Norway Research Fund, Spain: Fondo de Investigacion Santarias (grant codes 97/0035-01 , 99/0034-01 , and 99/0034-02 ), Hospital Universitario de Albacete, Consejeria de Sanidad, Barcelona: Sociedad Espanola de Neumología y Cirugía Toracica, Public Health Service (grant code R01 HL62633-01 ), Fondo de Investigaciones Santarias (grant codes 97/0035-01 , 99/0034-01 , and 99/0034-02 ), Consell Interdepartamentalde Recerca i Innovació Tecnológica (grant code 1999SGR 00241 ), Instituto de Salud Carlos III, Red de Centros de Epidemiología y Salud Pública, C03/09, Red de Bases moleculares y fisiológicas de las Enfermedades Respiratorias, C03/011 and Red de Grupos Infancia y Medio Ambiente G03/176, Huelva: Fondo de Investigaciones Santarias (grant codes 97/0035-01 , 99/0034-01 , and 99/0034-02 ), Oviedo: Fondo de Investigaciones Sanitaria ( 97/0035-02 , 97/0035 , 99/0034-01 , 99/0034-02 , 99/0034-04 , 99/0034-06 , 99/350 , and 99/0034-07 ), European Commission ( EU-PEAL PL01237 ), Generalitat de Catalunya ( CIRIT 1999 SGR 00214), Hospital Universitario de Albacete, Sociedad Española de Neumología y Cirugía Torácica ( SEPAR R01 HL62633-01 ), Red de Centros de Epidemiología y Salud Pública (C03/09), Red de Bases moleculares y fisiológicas de las Enfermedades Respiratorias (C03/011), and Red de Grupos Infancia y Medio Ambiente (G03/176, Sweden: Göteborg, Umea, AND Uppsala: Swedish Heart Lung Foundation, Swedish Foundation for Health Care Sciences and Allergy Research , Swedish Asthma and Allergy Foundation , Swedish Cancer and Allergy Foundation , and Swedish Council for Working Life and Social Research ( FAS ), Switzerland: Basel: Swiss National Science Foundation , Swiss Federal Office for Education and Science , and Swiss National Accident Insurance Fund, UK: Ipswich and Norwich: Asthma UK (formerly known as National Asthma Campaign)., Financial support for ECRHS I: The coordination of this work was supported by the European Commission , and the authors and participants are grateful to the late C. Baya and M. Hallen for their help during the study and K. Vuylsteek and the members of the COMAC for their support. The following grants helped to fund the local studies: Australia: Asthma Foundation of Victoria , Allen and Hanbury's, Belgium: Belgian Science Policy Office , National Fund for Scientific Research, Estonia: Estonian Science Foundation (grant no. 1088 ), France: Ministère de la Santé, Glaxo France , Institut Pneumologique d'Aquitaine , Contrat de Plan Etat-Région Languedoc-Rousillon , Caisse nationale de l'assurance maladie des travailleurs salariés, Comité national contre les maladies respiratoires et la tuberculose (90MR/10, 91AF/6), Ministre delegué de la santé, Réseau national de santé publique, France, Germany: Helmholtz Zentrum Munich and Bundesminister für Forschung und Technologie, Italy: Ministero dell'Università e della Ricerca Scientifica e Tecnologica, Consiglio Nazionale delle Ricerche, Regione Veneto (grant RSF no. 381/05.93 ), Portugal: Glaxo Farmacêutica Lda, Sandoz Portugesa, Spain: Fondo de Investigación Sanitaria (nos. 91/0016-060-05/E , 92/0319 , and 93/0393 ), Hospital General de Albacete, Hospital General Juan Ramón Jiménez, Dirección Regional de Salud Pública (Consejería de Sanidad del Principado de Asturias), Consell Interdepartamental de Recerca i Innovació Tecnològica (1997 SGR 00079), and Servicio Andaluz de Salud, Sweden: The Swedish Medical Research Council , the Swedish Heart-Lung Foundation , the Swedish Association against Asthma and Allergy, Switzerland: Swiss National Science Foundation (grant no. 4026-28099 ), and UK: National Asthma Campaign , British Lung Foundation , Department of Health , South Thames Regional Health Authority ., The ALEC study is funded by the European Union’s Horizon 2020 Research and Innovation programme under grant agreement number 633212. ISGlobal is a member of the CERCA Programme, Generalitat de Catalunya. National funders who supported data collection in the original studies are listed in Appendix E4 in this article's Online Repository at www.jaci-inpractice.org . The funders had no role in the writing of the manuscript or the decision to submit it for publication., Commission of the European Communities, Medical Research Council (MRC), and Ageing Lungs European Cohorts ALEC

Amanda J. Cross, Petra H.M. Peeters, Pietro Ferrari, Françoise Clavel-Chapelon, Salvatore Panico, Augustin Scalbert, Anja Olsen, José María Huerta, Paolo Vineis, Gianluca Severi, Eva Ardanaz, H. Bas Bueno-de-Mesquita, Ruth C. Travis, Bénédicte Elena-Herrmann, Nicholas J. Wareham, Pagona Lagiou, Talita Duarte-Salles, Christina Bamia, Anne Tjønneland, Rudolf Kaaks, Bodil Ohlsson, Magdalena Stepien, Antonio Agudo, Krasimira Aleksandrova, Heiner Boeing, Isabelle Romieu, Kay-Tee Khaw, Veronika Fedirko, Domenico Palli, Julie A. Schmidt, Anne Fages, Rosario Tumino, Valeria Pala, Anna Floegel, Dimitrios Trichopoulos, Miren Dorronsoro, Marc J. Gunter, Klas Sjöberg, Clément Pontoizeau, Marie-Christine Boutron-Ruault, Elisabete Weiderpass, Tilman Kühn, Elio Riboli, Mazda Jenab, Antonia Trichopoulou, Esther Molina-Montes, Fages, Anne, Duarte Salles, Talita, Stepien, Magdalena, Ferrari, Pietro, Fedirko, Veronika, Pontoizeau, Clément, Trichopoulou, Antonia, Aleksandrova, Krasimira, Tjønneland, Anne, Olsen, Anja, Clavel Chapelon, Françoise, Boutron Ruault, Marie Christine, Severi, Gianluca, Kaaks, Rudolf, Kuhn, Tilman, Floegel, Anna, Boeing, Heiner, Lagiou, Pagona, Bamia, Christina, Trichopoulos, Dimitrio, Palli, Domenico, Pala, Valeria, Panico, Salvatore, Tumino, Rosario, Vineis, Paolo, Bueno de Mesquita, H. Ba, Peeters, Petra H, Weiderpass, Elisabete, Agudo, Antonio, Molina Montes, Esther, Huerta, José María, Ardanaz, Eva, Dorronsoro, Miren, Sjöberg, Kla, Ohlsson, Bodil, Khaw, Kay Tee, Wareham, Nick, Travis, Ruth C, Schmidt, Julie A, Cross, Amanda, Gunter, Marc, Riboli, Elio, Scalbert, Augustin, Romieu, Isabelle, Elena Herrmann, Benedicte, Jenab, Mazda, ISA NMR Methods for Metabolism - Methodes RMN en métabolomique (2014-2018), Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), ISA - Centre de RMN à très hauts champs, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), parent, International Agency for Cancer Research (IACR), Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens], Department of Epidemiology, Deutsches Institut für Ernahrungsforschung Potsdam-Rehbrücke (DIFE), Institute of Cancer Epidemiology, Danish Cancer Society, Department of Food Science [Copenhagen] (UCPH FOOD), Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Gustave Roussy (IGR), Human Genetics Foundation (HuGeF), Università degli studi di Torino (UNITO), Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Thermo Fisher Scientific, Thermo Fisher Scientific Inc., German Institute of Human Nutrition Potsdam-Rehbruecke, German Institute of Human Nutrition, Harvard School of Public Health, WHO Collaborating Center for Food and Nutrition Policies, Department of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Nutritional Epidemiology Unit, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH)-IRCCS Foundation, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Cancer Registry and Histopathology Unit, Civile - M.P.Arezzo Hospital, Department of Epidemiology and Biostatistics, MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Julius Center for Health Sciences and Primary Care, VU University Medical Center [Amsterdam], Imperial College London-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Department of Community Medicine, University of Tromsø (UiT), Department of Research, Cancer Registry of Norway-Samfundet Folkhälsan, Helsinki, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet [Stockholm], Institut Català d'Oncologia, Spain Institute of Oncology, Andalusian School of Public Health [Granada], Consortium for Biomedical Research in Epidemiology and Public Health, CIBER de Epidemiología y Salud Pública (CIBERESP), Danish Cancer Society Research Center, Murcia Regional Health Council, Sección de Epidemiología de Enfermedades No Transmisibles, Navarre Public Health Institute, Epidemiology and Health Information, Public Health Department of Gipuzkoa, Volvo, VOLVO-VOLVO, Skane University Hospital [Lund], University of Cambridge School of Clinical Medicine, MRC epidemiology Unit, Addenbrooke's Hospital, Cancer Epidemiology Unit, University of Oxford [Oxford], Laboratoire d'informatique Fondamentale de Marseille (LIF), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), School of Public Health [London, UK] (Faculty of Medicine), Imperial College London, Department of Chemistry, University of Cambridge [UK] (CAM), Nutrition and Metabolism Section, Biomarkers Group, Nutrition and Metabolism Section, This work was supported by the French National Cancer Institute (L'Institut National du Cancer, INCA, grant number 2009-139, PI: M. Jenab). AF received financial support (BDI fellowship) from the Centre National de la Recherche Scientifique (CNRS) and Bruker Biospin. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark), Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, and Institut National de la Sante et de la Recherche Medicale (INSERM) (France), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ), and Federal Ministry of Education and Research (Germany), Hellenic Health Foundation (Greece), Italian Association for Research on Cancer (AIRC), National Research Council, Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (Italy), Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), and Statistics Netherlands (the Netherlands), European Research Council (ERC, grant number ERC-2009-AdG 232997) and Nordforsk, and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway), Health Research Fund (FIS), Regional Governments of Andalucia, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Skane and Vasterbotten (Sweden), Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK). The funders had no role in the study design, data collection, analysis, and interpretation presented in this article. They were neither involved in the writing of the manuscript, nor in the decision to submit it for publication., Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Centre Européen de Résonance Magnétique Nucléaire à Très Hauts Champs (CERMNTHC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 'Civile M. P. Arezzo' Hospital, Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), [Fages,A, Pontoizeau,C, Elena-Herrmann,B] Institut des Sciences Analytiques, Centre de RMN à très hauts champs, CNRS/ENS Lyon/UCB Lyon-1, Université de Lyon, Villeurbanne, France. [Duarte-Salles,T, Stepien,M, Ferrari,P, Scalbert,A, Romieu,I, Jenab,M] International Agency for Research on Cancer (IARC-WHO), Lyon, France. [Fedirko,V] Department of Epidemiology, Rollins School of Public Health, Winship Cancer Institute, Emory University, Atlanta, USA. [Trichopoulou,A] Hellenic Health Foundation, Athens, Greece. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece. [Aleksandrova,K, Floegel,A, Boeing,H] Department of Epidemiology, German Institute of Human Nutrition (DIfE), Potsdam-Rehbrücke, Germany. [Tjønneland,A, Olsen,A] Diet, Genes and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark. [Clavel-Chapelon,F, Boutron-Ruault,M] INSERM, Centre for Research in Epidemiology and Population Health (CESP), nutrition, Hormones and Women’s Health Team, Villejuif, France. Université Paris Sud, Villejuif, France. Institut Gustave Roussy, Villejuif, France. [Severi,G, Vineis,P] Human Genetics Foundation (HuGeF), Torino, Italy. [Kaaks,R, Kuhn,T] Department of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany. [Lagiou,P, Bamia,C] Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, Goudi, Athens, Greece. [Lagiou,P, Trichopoulos,D] Department of Epidemiology, Harvard School of Public Health, Boston, USA. [Palli,D] Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Florence, Italy. [Pala,V] Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. [Panico,S] Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy. [Tumino,R] Cancer Registry and Histopathology Unit, 'Civic - M.P. Arezzo' Hospital, Ragusa, Italy. [Vineis,P, Peeters,PH] MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK. [Bueno-de-Mesquita,HB] Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands. Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. [Bueno-de-Mesquita,HB, Cross,A, Gunter,M, RibolI,E] Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK. [Peeters,PH] Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. [Weiderpass,E] Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Samfundet Folkhälsan, Helsinki, Finland. [Agudo,A] Unit of Nutrition and Cancer, IDIBELL, Catalan Institute of Oncology-ICO, L’Hospitalet de Llobregat, Barcelona, Spain. [Molina-Montes,E] Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain. [Molina-Montes,E, Huerta,JM, Ardanaz, E] CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain. [Huerta,JM] Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain. [Ardanaz,E] Navarre Public Health Institute, Pamplona, Spain. [Dorronsoro,M] Public Health Direction and Biodonostia CIBERESP, Basque Regional Health Department, San Sebastian, Spain. [Sjöberg,K] Department of Clinical Sciences, Lund University, Malmö, Sweden. Department of Gastroenterology and Nutrition, Skåne University Hospital, Malmö, Sweden. [Ohlsson,B] Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital, Lund University, Malmö, Sweden. [Khaw,K] University of Cambridge School of Clinical Medicine, Clinical Gerontology Unit, Addenbrooke’s Hospital, Cambridge, UK. [Wareham,N] MRC Epidemiology Unit, University of Cambridge, Cambridge, UK. [Travis,RC, Schmidt,JA] Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK., This work was supported by the French National Cancer Institute (L’Institut National du Cancer, Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, and Institut National de la Santé et de la Recherche Médicale (INSERM) (France), Health Research Fund (FIS), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (No. 6236) and Navarra, and ISCIII RETIC (RD06/0020) (Spain), Swedish Cancer Society, Swedish Scientific Council, and Regional Government of Skåne and Västerbotten (Sweden), Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK). The funders had no role in the study design, data collection, analysis, and interpretation presented in this article. They were neither involved in the writing of the manuscript, nor in the decision to submit it for publication, Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Università degli studi di Torino = University of Turin (UNITO), University of Naples Federico II = Università degli studi di Napoli Federico II, and University of Oxford

Andrew S. Levey, Armando Teixeira-Pinto, Samuel Fung, Nicole Scholes-Robertson, Gloria Ashuntantang, Laura Cortés Sanabria, Samaya Anumudu, Amelie Bernier-Jean, Martin Howell, Louese Dunn, Tim Usherwood, Eduardo Lorca, Martin Wilkie, Andrea Matus Gonzalez, Magdalena Madero, Ikechi G. Okpechi, Daniel Gallego, Jonathan C. Craig, Adeera Levin, Allison Tong, Patrick Rossignol, Katherine Widders, Yeoungjee Cho, Ian H. de Boer, Andrea K. Viecelli, David C. Wheeler, Nicole Evangelidis, Bénédicte Sautenet, Laura Sola, Chandana Guha, The University of Sydney, Westmead Hospital [Sydney], MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Instituto Nacional de Cardiologia Ignacio Chavez, Université de Yaoundé I, Hospital Universitario de Guadalajara, Department of Medicine, Kidney Research Institute, University of Washington, Kidney Research Institute [Seattle] (KRI), Princess Margaret Hospital, Hong Kong, Federacion Nacional ALCER (Spanish Kidney Patient's Federation), Tufts University School of Medicine [Boston], University of British Columbia (UBC), Hospital Salvador, University of Cape Town, University of Alberta, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Dialysis Unit, CASMU-IAMPP, Montevideo, University of New South Wales [Sydney] (UNSW), Centre for Nephrology, UCL Medical School, Translational Research Institute, University College of London [London] (UCL), University of Queensland [Brisbane], Princess Alexandra Hospital, Brisbane, Baylor College of Medecine, Sheffield Children's NHS Foundation Trust, Flinders University [Adelaide, Australia], This project is supported by the National Health and Medical Research Council (NHMRC) Program Grant 1092597. NE is supported by the National Health and Medical Research Council (NHMRC) Program Grant 1092597. AT is supported by The University of Sydney Robinson Fellowship. YC is supported by the NHMRC Early Career Fellowship 1126256. AV is supported by a Jacquot Research Establishment Fellowship. The funding bodies do not have a role in the design, collection, analysis, and interpretation of data, in the writing of the manuscript, and in the decision to submit the manuscript for publication., Division of Nephrology and Hypertension, Faculty of Health Sciences, Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, and BOZEC, Erwan

Patrice Cacoub, Gilles Berrut, Olivier Hanon, Tahar Chouihed, Nicholas Lamblin, Nicholas Delarche, Emmanuel Andrès, Patrick Henry, Thibaud Damy, CHU Henri Mondor, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Centre hospitalier de Pau, Pôle hospitalo-universitaire de gérontologie clinique [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Immunologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, CHU Strasbourg, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Université de Paris (UP), Novartis provided financial support for logistic management but was not involved in the writing of the manuscript., CHU Henri Mondor [Créteil], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Université Paris Cité (UPCité), and Gestionnaire, HAL Sorbonne Université 5

Raphaëlle Delpech, Isabelle Pendola-Luchel, Pascaline Mourey, Mathilde Baumhauer, Arnaud Gautier, Henri Panjo, Rissane Ourabah, Lorraine Poncet, L. Rigal, Virginie Ringa, 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, This project was funded by the French Research Institute in Public Health (IReSP). The funder had no role in the creation of the research question, design of the study, data collection, analysis, interpretation, or in the writing of this manuscript., Santé publique France - French National Public Health Agency [Saint-Maurice, France], Institut national d'études démographiques (INED), Université Paris-Saclay, and HAL UVSQ, Équipe

Stéphanie Vandentorren, Yvon Motreff, Maude Marillier, Gabrielle Rabet, Thierry Baubet, Cécile Vuillermoz, Lise Eilin Stene, Antoine Messiah, Philippe Pirard, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ministère des Affaires Sociales et de la Santé PIA ANR-10-EQPX-0021-01 Norges Forskningsråd: 288321, and This study was performed by Santé publique France as part of its remit. Santé publique France is funded by the French Ministry of Health. The ESPA 13 November survey is part of EQUIPEX Matrice’s '13 November' transdisciplinary research programme which is funded by the French General Secretariat for investment (SGPI) via the National Research Agency (ANR) and its 'Programme d’Investissement pour l’Avenir' (PIA ANR-10-EQPX-0021-01). PP, YM, GR, MM and SV are employees of Santé publique France. AM and TB are employees of the 'Institut National de la Santé et de la Recherche Médicale'. The contributions from LES and CV were funded by The Research Council of Norway (p.nr. 288321). The funding bodies had no role in the design of the study, data collection, data analysis, data interpretation or in the writing of the manuscript. Acknowledgments

Véronique Phé, Charles Joussain, Karel Everaert, Rebecca Haddad, Thomas F. Monaghan, G. Robain, Saskia Roggeman, Wendy Bower, Hôpital Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine physique et réadaptation [CHU Raymond-Poincaré], Hôpital Raymond Poincaré [AP-HP], Sorbonne Université - Département de neurologie 2 - Mazarin, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Société Française de Médecine Vasculaire, SFMV, and RH reports grants from, Fonds de dotation Renaitre, Société Française de Médecine Physique et de Réadaptation with the institutional support of Merz Pharma France and Société Interdisciplinaire Francophone d’UroDynamique et de Pelvi Périnéologie. Authors independently conceptualized the design, methods, data collection, analysis and writing of the manuscript and grants did not influence the content.

Marc Leone, Jacques Duranteau, Eric Vicaut, François Dépret, Daniel De Backer, Matthieu Legrand, Bruno Levy, Patrick Rossignol, Hafid Ait Oufella, Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Service d'Anesthésie-Réanimation [AP-HP Hôpitaux Saint-Louis Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Université Sorbonne Paris Nord, French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), University of California [San Francisco] (UCSF), University of California, Université Pierre et Marie Curie - Paris 6 (UPMC), Centre Hospitalier Interrégional Edith Cavell (CHIREC), Hôpitaux Universitaires Paris Sud, Hôpital Nord AP‐MM Marseille, France (AP‐MM Marseille), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Service de Réanimation Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Université de Lorraine (UL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), The study is funded by a grant from the Programme Hospitalier de Recherche Clinique - PHRC National 2017 from the French Minister of Health. The funding body has no role in the design of the study, collection, analysis, and interpretation of the data, and writing of the manuscript., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), University of California [San Francisco] (UC San Francisco), University of California (UC), Service d'Anesthésie réanimation [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université libre de Bruxelles (ULB), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Assistance Publique - Hôpitaux de Marseille (APHM), Université de Lorraine (UL), and BOZEC, Erwan

Jean-Marc Collard, Perlinot Herindrainy, Raymond Bercion, Didier Guillemot, Maria Pardos de la Gandara, Andriniaina Rakotondrasoa, Benoit Garin, Elisabeth Delarocque-Astagneau, Agathe de Lauzanne, Melanie Hennart, Sylvain Brisse, Carla Rodrigues, Virginie Passet, Thierno Abdoulaye Diallo, Muriel Vray, Bich-Tram Huynh, Alexandra Kerleguer, Laurence Borand, Abdoulaye Seck, Biostatistique, Biomathématique, Pharmacoépidémiologie et Maladies Infectieuses (B2PHI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, Institut Pasteur [Paris], Unité de Bactériologie Expérimentale [Antananarivo, Madagascar] (IPM), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut Pasteur de Dakar, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur du Cambodge, Institut Pasteur de Bangui, Centre National de Référence - National Reference Center Escherichia coli, Shigella et Salmonella (CNR-ESS), This work was supported by the Institut Pasteur programme Action Concertee Inter-Pasteurienne (Grant A-14-2014) and by the French government’s Investissement d’Avenir program Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant ANR-10-LABX-62-IBEID). Support to the BIRDY project was provided by the Total Foundation, MSDAVENIR and the Monaco Department of International Cooperation. CR was supported financially by the MedVetKlebs project, a component of European Joint Programme One Health EJP, which has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No 773830. The funders had no role in study design, data collection and analysis, interpretation, or writing of the manuscript., We thank all collaborators of the BIRDY program: Rasoanaivo Fanjalalaina Vololonirina, Andrianonimiadana Lova Maminirina, Rabearitiana Lydos, Rasoloson Dimitri, Randrianirina Frédérique, Ratsima Hariniaina Elisoa, Volahasina Antsa Tanjona, Volahasina Antso Fenitra, Randriamamonjiarison Aina Nirina, Andrianirina Zafitsara Zo, Andriatahina Todisoa, Vincent Richard, Awa Ndir, Amy Gassama Sow, Balla Sy, Marguerite Diatta, Pape Samba Dieye, Jean Baptiste Diouf, Joseph Faye, Abibatou Ndiaye, Bouya Ndao, Thida Chon, Veronique Ngo, Arnaud Tarantola, Sok Touch, Patrice Piola, Sophie Goyet, Siyin Lach, Elsa Kermorvant-Duchemin, Michael Padget, Laurence Watier, and Abdou Armya Youssouf. We thank all physicians, laboratory staff, field interviewers, and community workers involved in the project. We thank Leonardo Panunzi for assistance with genomic analyses of resistance genes, and the 'Plateforme de Microbiologie Mutualisée' of Institut Pasteur for genomic sequencing. We are grateful to all women participating in the BIRDY program., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 773830,H2020-SFS-2017-1,MedVetKlebs (a component of European Joint Programme One Health EJP)(2018), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), European Project: 773830,H2020-SFS-2017-1,MedVetKlebs (a component of European Joint Programme One Health)(2018), Moulherat, Isabelle, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, and Klebsiella pneumoniae: from ecology to source attribution and transmission control - MedVetKlebs (a component of European Joint Programme One Health) - - H2020-SFS-2017-12018-01-01 - 2019-12-31 - 773830 - VALID

Josep A. Tur, Itziar Abete, José J. Gaforio, Jordi Salas-Salvadó, Nerea Becerra-Tomás, Francisco J. Tinahones, Albert Goday, Xavier Pintó, Maria Dolors Zomeño, Julia Wärnberg, Alejandro Oncina-Canovas, Carmen Saiz, Jessica Pérez-López, Dolores Corella, Clotilde Vázquez, Lucas Tojal-Sierra, Leyre Notario-Barandiaran, Marga Morey, Lidia Daimiel, Aurora Bueno-Cavanillas, José Manuel Santos-Lozano, José Lapetra, F. Javier Basterra-Gortari, Julia Muñoz, Alicia Julibert, Marian Martín, M. Rosa Bernal-Lopez, Sara Castro-Barquero, Ana Galera, Josep Vidal, Vicente Martín-Sánchez, Miguel Ruiz-Canela, Maria C Belló-Mora, Emilio Ros, Ignacio M. Gimenez-Alba, Antonio García Ríos, Tamara Casañas-Quintana, Ángel M. Alonso-Gómez, Jesús García-Gavilán, Josep Basora, Jesús Vioque, Ramon Estruch, Dora Romaguera, Luis Serra-Majem, Cesar I Fernandez-Lazaro, Pilar Matía-Martín, Escarlata Angullo-Martinez, Cristina Bouzas, Carmen Sayón-Orea, J. Alfredo Martínez, Olga Castañer, Maria del Mar Bibiloni, [Bouzas,C, Bibiloni,MM, Julibert,A, Ruiz-Canela,M, Salas-Salvadó,J, Corella,D, Zomeño,MD, Romaguera,D, Alonso-Gómez,ÁM, Wärnberg,J, Martínez,JA, Serra-Majem,L, Estruch,R, Tinahones,FJ, Lapetra,J, Pintó,X, García Ríos,A, Vázquez,C, Ros,E, Fernandez-Lázaro,CI, Becerra-Tomás,N, Gimenez-Alba,IM, Muñoz,J, Morey,M, Pérez-López,J, Abete,I, Casañas-Quintana,T, Castro-Barquero,S, Bernal-López,MR, Santos-Lozano,JM, Galera,A, Angullo-Martinez,E, Basterra-Gortari,FJ, Basora,J, Saiz,C, Castañer,O, Martín,M, Belló-Mora,MC, Sayón-Orea,C, García-Gavilán,J, Goday,A, Tur,JA] CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Bouzas,C, Tojal-Sierra,L, Tur,JA] Research Group on Community Nutrition & Oxidative Stress, University of Balearic Islands, Guillem Colom Bldg, Campus, Palma de Mallorca, Spain. [Bouzas,C, Tur,JA] Health Research Institute of the Balearic Islands (IdISBa), Palma de Mallorca, Spain. [Ruiz-Canela,M, Sayón-Orea,C] Department of Preventive Medicine and Public Health, IdISNA, University of Navarra, Pamplona, Spain. [Salas-Salvadó,J, García-Gavilán,J] Universitat Rovira i Virgili, Department of Biochemistry and Biotechnology, Human Nutrition Unit, Reus, Spain. [Salas-Salvadó,J] Institut d’Investigació Sanitària Pere Virgili (IISPV), Reus, Spain. [Corella,D, Saiz,C] Department of Preventive Medicine, University of Valencia, Valencia, Spain. [Zomeño,MD, Goday,A] Unit of Cardiovascular Risk and Nutrition, Institut Hospital del Mar de Investigaciones Médicas Municipal d’Investigació Mèdica (IMIM), Barcelona, Spain. [Zomeño,MD] Blanquerna School of Health Sciences, Universitat Ramon Llull, Barcelona, Spain. [Vioque,J, Oncina-Canovas,A, Notario-Barandiarán,L] Unit of Nutritional Epidemiology, Miguel Hernández University, ISABIAL-UMH, Alicante, Spain. [Vioque,J, Bueno-Cavanillas,A, Gaforio,JJ, Notario-Barandiarán,L] CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Alonso-Gómez,ÁM, Belló-Mora,MC] Bioaraba Health Research Institute, Osakidetza Basque Health Service, Araba University Hospital, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain. [Wärnberg,J, Pérez-López,J] Department of Nursing, School of Health Sciences, University of Málaga-IBIMA, Málaga, Spain. [Martínez,JA] Precision Nutrition Program, IMDEA Food, CEI UAM + CSIC, Madrid, Spain. [Martínez,JA, Abete,I] Department of Nutrition, Food Sciences, and Physiology, Center for Nutrition Research, University of Navarra, Pamplona, Spain. [Serra-Majem,L, Casañas-Quintana,T] Institute for Biomedical Research, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain. [Estruch,R, Castro-Barquero,S] Department of Internal Medicine, IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain. [Tinahones,FJ, Bernal-López,MR] Virgen de la Victoria Hospital, Department of Endocrinology, Biomedical Research Institute of Málaga (IBIMA), University of Málaga, Málaga, Spain. [Lapetra,J, Santos-Lozano,JM] Department of Family Medicine, Research Unit, Distrito Sanitario Atención Primaria Sevilla, Sevilla, Spain. [Pintó,X, Galera,A] Lipids and Vascular Risk Unit, Internal Medicine, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona, Spain. [García Ríos,A] Lipids and Atherosclerosis Unit, Department of Internal Medicine, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain. [Bueno-Cavanillas,A] Department of Preventive Medicine, University of Granada, Granada, Spain. [Gaforio,JJ] Department of Health Sciences, Centro de Estudios Avanzados en Olivar y Aceites de Oliva, University of Jaen, Jaen, Spain. [Matía-Martín,P] Department of Endocrinology and Nutrition, Instituto de Investigación Sanitaria Hospital Clínico San Carlos (IdISSC), Madrid, Spain. [Daimiel,L] Nutritional Genomics and Epigenomics Group, IMDEA Food, CEI UAM + CSIC, Madrid, Spain. [Martín-Sánchez,V] CIBER Diabetes y Enfermedades Metabólicas (CIBERDEM), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. [Martín-Sánchez,V] Institute of Biomedicine (IBIOMED), University of León, León, Spain. [Vidal,J] Department of Endocrinology, IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Spain. [Vázquez,C] Department of Endocrinology, Fundación Jiménez-Díaz, Madrid, Spain. [Ros,E] Lipid Clinic, Department of Endocrinology and Nutrition, Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain. [Angullo-Martinez,E] Escola Graduada Primary Health Care Center, IBSalut, Palma de Mallorca, Spain. [Basterra-Gortari,FJ, Sayón-Orea,C] Servicio Navarro de Salud, Osasunbidea, Pamplona, Spain., The PREDIMED-Plus trial was supported by the official funding agency for biomedical research of the Spanish government, ISCIII, through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (five coordinated FIS projects led by J.S.-S. and J.Vidal, including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, and PI19/01332, the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to J.S.-S., the European Research Council (Advanced Research Grant 2013–2018, 340918) to Miguel Ángel Martínez-González, the Recercaixa Grant to J.S.-S. (2013ACUP00194), Grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, and PI0137/2018), a Grant from the Generalitat Valenciana (PROMETEO/2017/017), a SEMERGEN Grant, EU-COST Action CA16112, a Grant of support to research groups no. 35/2011 from the Balearic Islands Government, Grants from Balearic Islands Health Research Institute (IDISBA), funds from the European Regional Development Fund (CIBEROBN CB06/03 and CB12/03) and from the European Commission (EAT2BENICE_H2020_SFS2016). M. Rosa Bernal-López was supported by 'Miguel Servet Type I' program (CP15/00028) from the ISCIII-Madrid (Spain), cofinanced by the European Regional Development Fund. Jordi Salas-Salvadó is partially supported by ICREA under the ICREA Academia programme. Cristina Bouzas received a Fernando Tarongí Bauzà PhD Grant. I.M Gimenez-Alba received a grant FPU from the Ministry of Science, Innovation and Univesities (reference FPU 18/01703). The funding sponsors had no role in the design of the study, in the collection, analyses, or interpretation of the data, and in the writing of the manuscript, and in the decision to publish the results.

Thorarinn Gislason, Isabelle Pin, Nicole Probst-Hensch, Jesús Martínez-Moratalla, Bénédicte Leynaert, Alessandro Marcon, Judith Garcia-Aymerich, Sandra Dorado-Arenas, Pascal Demoly, Rain Jõgi, Deborah Jarvis, Joachim Heinrich, Torben Sigsgaard, Josep M. Antó, Eva Lindberg, Jose Antonio Gullón-Blanco, Elisabeth Zemp, Dennis Nowak, Chantal Raherison, Kai Triebner, Shyamali C. Dharmage, Diana A van der Plaat, José Luis Sánchez-Ramos, Kjell Torén, Bertil Forsberg, Giancarlo Pesce, Steinar Hustad, Francisco Gómez-Real, Dominique Courbon, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Bergen (UiB), National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Aarhus University Hospital, Institute of Epidemiology [Neuherberg] (EPI), German Research Center for Environmental Health - Helmholtz Center München (GmbH), IMIM-Hospital del Mar, Generalitat de Catalunya, Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA), Université Bordeaux Segalen - Bordeaux 2-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), BrainTech Laboratory [CHU Grenoble Alpes - Inserm U1205] (Brain Tech Lab ), CHU Grenoble-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Sahlgrenska Academy at University of Gothenburg [Göteborg], Umeå University, Uppsala University Hospital, University of Basel (Unibas), Imperial College London, Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Agence Nationale de la Recherche, ANR 633212 Comité des Maladies Respiratoires de l'Isère European Commission, EC: QLK4-CT-1999–01237 Norges ForskningsrÃ¥d: 228174 Institut National de la Santé et de la Recherche Médicale, Inserm: U700 Agence Nationale de la Recherche, ANR Medical Research Council, MRC: 92091 Composites Innovation Centre, CIC Eesti Teadusagentuur: 562, The current study is part of the Ageing for Lungs in European Cohorts (ALEC) study ( www.alecstudy.org ), ALEC has received funding from the European Union's Horizon 2020 research and innovation program [grant agreement No. 633212]. The coordination of the ECRHS was supported by the European Commission [grant agreement no. QLK4-CT-1999–01237] and the Medical Research Council [grant agreement no. 92091]. The hormones measures at ECRHS III were funded by the Norwegian Research Council [grant agreement no. 228174]. Hormones measures at ECRHS II were funded by the local budget of the ECRHS Paris team, INSERM U700, Epidemiology, with further support from the Comité National contre les Maladies Respiratoires (CNMR), the centre d'Investigation Clinique (CIC), Bichat Hospital, and the French Agence Nationale de la Recherche (ANR). Bodies funding the local studies are listed in the Online Supplement. The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication., Dr Demoly reports presentation honoraria from Stallergène Greer, ALK, Mylan, Astra Zeneca, Bausch&Lomb and personal fees as board advisor from Chiesi, Sanofi, Thermo Fisher Scientific, outside the submitted work. Dr Jogi reports personal grants from the Estonian Research Council [personal research grant no.562], and reports travel grants and presentation honoraria from GSK, Novartis, Boehringer, outside the submitted work. Dr Pin reports travel grants and presentation honoraria from GSK, Novartis, Astra Zeneca, Zambon Pharma, outside the submitted work. All the authors declare no competing interests., European Project: 633212,H2020,H2020-PHC-2014-two-stage,ALEC(2015), Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)

Barré, Tangui, Nishimwe, Marie Libérée, Protopopescu, Camelia, Marcellin, Fabienne, Carrat, Fabrice, Dorival, Céline, Delarocque-Astagneau, Elisabeth, Larrey, Dominique G., Bourlière, Marc, Petrov-Sanchez, Ventzislava, Simony, Mélanie, Pol, Stanislas, Fontaine, Hélène, Carrieri, Patrizia Maria, Pageaux, Georges Philippe, HAL UVSQ, Équipe, Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Observatoire régional de la santé Provence-Alpes-Côte d'Azur [Marseille] (ORS PACA), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Biostatistique, Biomathématique, Pharmacoépidémiologie et Maladies Infectieuses (B2PHI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'hépatologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Merck Sharp and Dohme, MSD Agence Nationale de la Recherche, ANR AbbVie Bristol-Myers Squibb, BMS AbbVie Association Française pour l'Etude du Foie, AFEF Roche Gilead Sciences Shionogi Cilag MSD France, FC reports grants from INSERM-ANRS, during the conduct of the study, and personal fees from Imaxio, outside the submitted work. MB reports grants and personal fees from AbbVie and Gilead, outside the submitted work, and personal fees from MSD, Janssen, Boehringher Ingelheim, Intercept, and Bristol-Myers Squibb, outside the submitted work. SP has received consulting and lecturing fees from Bristol-Myers Squibb, Janssen, Gilead, Roche, MSD, MYR-Pharma, Shionogi, Biotest and Abbvie, as well as grants from Bristol-Myers Squibb, Gilead, Roche and MSD. HF reports personal fees and invitations for medical meetings from Gilead, AbbVie, Bristol-Myers Squibb, MSD, and Janssen, outside the submitted work. Other authors declare no financial support. The cohort received financial support from the INSERM-ANRS (France Recherche Nord & Sud Sida-HIV H?patites), the French ANR (Agence Nationale de la Recherche), the French DGS (Direction Générale de la Santé), Merck Sharp and Dohme, Janssen-Cilag, Gilead, Abbvie, Bristol-Myers Squibb, and Roche. Those funding sources had no role in the writing of the manuscript or the decision to submit it for publication. We thank the study participants and the participating clinicians at each site. We also thank the INSERM-ANRS for sponsoring, funding and conducting the ANRS CO22 Hepather cohort in collaboration with the French Association for the Study of the Liver (Association Fran?aise pour l'Etude du Foie: AFEF). Finally, our thanks to Jude Sweeney for the English revision and editing of our manuscript., On behalf of the ANRS/AFEF Hepather study group : Delphine Bonnet, Virginie Sicart (CHU Purpan, Toulouse, France), François Bailly, Marjolaine Beaudoin, Dominique Giboz, Kerstin Hartig‐Lavie, Marianne Maynard (Hospices Civils de Lyon, Lyon, France), Morane Cavellec, Marjorie Cheraud‐Carpentier, François Raffi, Florian Vivrel (Hôpital Hôtel‐Dieu, Nantes, France), Jaouad Benhida, Jérôme Boursier, Paul Calès, Françoise Lunel, Frédéric Oberti (CHU Angers, Angers, France), Nathalie Boyer, Audrey Gilibert, Nathalie Giuily (Hôpital Beaujon, Clichy, France), Giovanna Scoazec (Hôpital Beaujon, Clichy, France and Hôpital Henri Mondor, Créteil, France), Sandrine Fernandes, Sylvie Keser, Philippe Sultanik, Anaïs Vallet‐Pichard (Hôpital Cochin, Paris, France), Juliette Foucher, Jean‐Baptiste Hiriart, Aurore Mathias, Julien Vergniol (Hôpital Haut‐Lévêque, Pessac, Bordeaux, France), Chrystelle Ansaldi, Laëtitia Chouquet, Emilie De Luca, Valérie Oules (Hôpital Saint Joseph, Marseille, France), Rodolphe Anty, Eve Gelsi, Régine Truchi (CHU de Nice, Nice, France), Elena Luckina, Nadia Messaoudi, Joseph Moussali, (Groupe Hospitalier Pitié‐Salpétrière, Paris, France), Barbara De Dieuleveult, Damien Labarriere, Pascal Poter, Si Nafa Si Ahmed (CHR La Source, Orléans, France), Nathalie Ganne‐Carrié, Véronique Grando‐Lemaire, Pierre Nahon, Alan Peltier, Judith Ung (Hôpital Jean Verdier, Bondy, France), Mariette Gougeon, Anne Guillygomarch, Caroline Jezequel (CHU Rennes, Rennes, France), Romain Moirand, Thomas F. Baumert, Michel Dofföel, Catherine Mutter, Pauline Simo‐Noumbissie (Hôpitaux Universitaires de Strasbourg, Strasbourg, France), Hélène Barraud, Mouni Bensenane, Abdelbasset Nani, Sarah Hassani‐Nani (CHU de Nancy, Vandoeuvre‐lès‐Nancy, France), Marie‐Albertine Bernard (CHU de Nancy, Vandoeuvre‐lès‐Nancy, France and Centre Hospitalier Régional, Metz, France), Michael Bismuth, Ludovic Caillo, Stéphanie Faure, Georges‐Philippe Pageaux, Marie Pierre Ripault (Hôpital Saint Eloi, Montpellier, France), Karl Barange, Christophe Bureau, Jean Marie Peron, Marie Angèle Robic, Léa Tarallo (CHU Purpan, Toulouse, France), Marine Faure, Bruno Froissart, Marie‐Noelle Hilleret, Vincent Leroy (CHU de Grenoble, Grenoble, France), Odile Goria, Victorien Grard, Hélène Montialoux (CHU Charles Nicolle, Rouen, France), Muriel François, Christian Ouedraogo, Christelle Pauleau, Anne Varault (Hôpital Henri Mondor, Créteil, France), Tony Andreani, Bénédicte Angoulevant, Azeline Chevance, Lawrence Serfaty (Hôpital Saint‐Antoine, Paris, France), Teresa Antonini, Audrey Coilly, Jean‐Charles Duclos Vallée, Mariagrazia Tateo (Hôpital Paul Brousse, Villejuif, France), Armand Abergel, Corinne Bonny, Chanteranne Brigitte, Géraldine Lamblin, Léon Muti (Hôpital Estaing, Clermont‐Ferrand, France), Abdenour Babouri, Virginie Filipe (Centre Hospitalier Régional, Metz, France), Camille Barrault, Laurent Costes, Hervé Hagège, Soraya Merbah (Centre Hospitalier Intercommunal, Créteil, France), Paul Carrier, Maryline Debette‐Gratien, Jérémie Jacques (CHU Limoges, Limoges, France), Florent Artu, Valérie Canva, Sébastien Dharancy, Alexandre Louvet (CHRU Claude Huriez, Lille, France), Marc Bardou, Donya Da Costa Souhiel, Patrick Hillon, Marianne Latournerie (Dijon University Hospital, Dijon, France), Yannick Bacq, Didier Barbereau, Charlotte Nicolas (CHU Trousseau, 37044 Tours, France), Nisserine Ben Amara, Danièle Botta‐Fridlund, Isabelle Portal (CHU Timone, Marseille, France), Moana Gelu‐Simeon, Marie‐Josée Lafrance (CHU de Pointe‐à‐Pitre, Pointe‐à‐Pitre, Guadeloupe)., Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Eloi, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)

Minoarisoa Rajerison, Benoit Garin, Soanandrasana Rahelinirina, Fehivola Andriamiaramanana, Pascale Bourhy, Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP), Biologie des Spirochètes / Biology of Spirochetes, Institut Pasteur [Paris], CHU Pointe-à-Pitre/Abymes [Guadeloupe], We would like to thank the staff of the Plague Unit, Institut Pasteur Madagascar for field and technical assistance, and the team of the Centre National de Référence de la Leptospirose, Institut Pasteur, Paris for technical assistance genotyping isolates. We thank D. Wagner for improving the English writing in the manuscript., and Institut Pasteur [Paris] (IP)

Damien Batalie, Thomas Montange, Richard Njouom, Edouard Betsem, Caroline Lambert, Antoine Gessain, Augustin Mouinga-Ondémé, Florence Buseyne, Epidémiologie et Physiopathologie des Virus Oncogènes (EPVO (UMR_3569 / U-Pasteur_3)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Cellule Pasteur, PRES Sorbonne Paris Cité-Université Paris Diderot - Paris 7 (UPD7), Université de Yaoundé I [Yaoundé], Centre international de recherches médicales de Franceville (CIRMF), Organisation Mondiale de la Santé (OMS), Centre Pasteur du Cameroun, Réseau International des Instituts Pasteur (RIIP), C.L. was personally supported by a doctoral grant from the French government program Investissement d’Avenir, Laboratory of Excellence, Integrative Biology of Emerging Infectious Diseases (LabEx IBEID). This study was supported by the Institut Pasteur in Paris, France, the Program Transversal de Recherche from the Institut Pasteur (PTR#437), and the Agence Nationale de la Recherche (grant ANR-10-LABX-62-IBEID, REEMFOAMY project, ANR 15-CE-15-0008-01). The funding agencies had no role in the study design, generation of results, or writing of the manuscript., We thank M. Bourgine for her helpful advice on the ELISAs. We thank members of the Unité d’Épidémiologie et Physiopathologie des Virus Oncogènes for discussions and technical advice. The text has been edited by a native English speaker., ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010), ANR-15-CE15-0008,REEMFOAMY,L'infection humaine par les virus foamy simiens zoonotiques : rôle des facteurs virologiques et immunologiques dans la restrcition de l'emergence virale(2015), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Université de Yaoundé I, Centre International de Recherches Médicales de Franceville (CIRMF), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris]

Lisa V. Hampson, Marie-Cécile Le Deley, Caroline Brard, Nathalie Gaspar, Gwénaël Le Teuff, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Statistical Methodology [Bâle, Suisse], Novartis Pharma AG, Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Institut Gustave Roussy (IGR), Unité de Méthodologie et de Biostatistique [Lille] (UMB), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, We acknowledge for the design, analysis, interpretation of the simulation study, and for the writing of the manuscript, funding from – PhD grant from doctoral school of public health, Paris-Sud, Paris-Saclay – Lisa Hampson’s contribution to the paper was partly funded by the UK Medical Research Council (grant MR/M013510/1) and was completed while she was an employee of Lancaster University – Ligue contre le cancer, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER, and Bodescot, Myriam

Ariza Aguila, Marianette T. Inobaya, Ava Kristy Sy, Edward K. Thomsen, Jason R. Angeles, Michael J. Bangs, Ferdinand V. Salazar, Richard Paul, Tom Toner, Research Institute for Tropical Medicine [Muntinlupa City, Philippines], Liverpool School of Tropical Medicine (LSTM), Kasetsart University - KU (THAILAND), Kasetsart University (KU), PT Freeport Indonesia/International SOS, Génétique fonctionnelle des maladies infectieuses - Functional Genetics of Infectious Diseases, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Génomique évolutive, modélisation et santé (CNRS-UMR2000), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), This study was funded by the Agence Française de Développement in the context of the Ecomore 2 programme ( www.ecomore.org/ ). The funding body did not have any role in project design or in the writing of this manuscript. The trial sponsor is Institut Pasteur, Paris, France., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Génomique évolutive, modélisation et santé (GEMS)

Jacqueline Milet, Michel Cot, André Garcia, Florence Bodeau-Livinec, Amanda Garrison, David Courtin, Pierre Ayotte, Achille Massougbodji, Babak Khoshnood, Equipe 1 : EPOPé - Épidémiologie Obstétricale, Périnatale et Pédiatrique (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Institut de Recherche Clinique du Bénin [Abomey-Calavi, Bénin] (IRCB), Institut National de Santé Publique du Québec [Canada] (INSPQ), École des Hautes Études en Santé Publique [EHESP] (EHESP), The Eunice Kennedy Shriver National Institute of Child Health & Human Development (NIH/NICHD) funded the TOVI study, grant R21-HD060524. The MiPPAD trial (NCT00811421) was co-funded by the European and Developing Countries Clinical Trials Partnership (EDCTP-IP.07.31080.002). The 'Anaemia in Pregnancy: Etiologies and Consequences' (APEC) study received funding from a grant from the Bill and Melinda Gates Foundation. The TOLIMMUNPAL project was funded by the French ANR (Agence Nationale de la Recherche) and coordinated by Dr André Garcia (IRD, UMR 216). Amanda Garrison received funding from PRINCEPS (Université Sorbonne Paris Cité) during the writing of this manuscript., ANR-10-PRSP-0012,TOLIMMUNPAL(2010), Bodescot, Myriam, PROGRAMME DE RECHERCHE EN SANTE PUBLIQUE - - TOLIMMUNPAL2010 - ANR-10-PRSP-0012 - PRSP - VALID, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), and Mère et enfant face aux infections tropicales (MERIT - UMR_D 216)

Marion Richard, Didier Hocquet, Didier Mazel, Christine Fagnoni-Legat, Virginie Nerich, Alexandre Meunier, Xavier Bertrand, Olivier Adotevi, Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de radiologie et d'Imagerie médicale diagnostique et thérapeutique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de pharmacologie, Plasticité du Génome Bactérien - Bacterial Genome Plasticity (PGB), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), This work was supported by the University Hospital of Besançon, France (Grant RAPACE - APICHU 2016). The study sponsor had no role in the design of the study, the collection, analysis and interpretation of the data, the writing of the manuscript or the decision to submit the manuscript for publication, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Hôpital Jean Minjoz, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Service de pharmacie, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Université de Franche-Comté (UFC)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM), and Plasticité du Génome Bactérien

Anne-Claire Andries, Anavaj Sakuntabhai, Veasna Duong, Sivuth Ong, Philippe Dussart, Paul F. Horwood, Philippe Buchy, Sopheaktra Ros, Unité de Virologie / Virology Unit [Phnom Penh], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Génétique fonctionnelle des Maladies infectieuses - Functional Genetics of Infectious Diseases, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), The study was supported by Standard Diagnostics, Inc. The funders had no role in study design, in the collection, analysis and interpretation of data, in writing of the manuscript, or in the decision to submit the article for publication. This research also received funding from the European Union Seventh Framework Programme (FP7/2007/2011) under Grant Agreement n°282 378., European Project: 282378,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,DENFREE(2012), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]

Phum Souy, Narann Tops, Saorin Kim, Khem Kosal, Eva Christophel, Chan Vanna, Sinoun Muth, Khon Sothea, Didier Menard, Pascal Ringwald, Sim Kheng, Chuor Meng Char, Po Ly, Alexandra Kerleguer, Walter R. J. Taylor, Pety Tor, Virak Khieu, John Kevin Baird, Steven Bjorge, National Center for Parasitology, Entomology and Malaria Control [Phnom Penh, Cambodia] (CNM), Service de Médecine Tropicale et Humanitaire [Geneva, Suisse], Hôpitaux Universitaires de Genève (HUG), Mahidol Oxford Tropical Medicine Research Unit, University of Oxford [Oxford]-Mahidol University [Bangkok], World Health Organization [Phnom Penh] (WHO), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Pailin Referral Hospital [Pailin, Cambodge], Anlong Veng Referral Hospital [Anlong Venh, Cambodge]., Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Pramoy Health Centre [Cambodia], Eijkman Oxford Clinical Research Unit [Jakarta, Indonesie], Eijkman Institute of Molecular Biology [Jakarta, Indonesie], Centre for Tropical Medicine and Global Health [Oxford, UK], Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford [Oxford]-University of Oxford [Oxford], Regional Office of the Western Pacific (WHO), Funding for this study was obtained by PR of WHO Geneva via a grant from UKAid without which this study would not have taken place. We record our profound gratitude to the taxpayers of the United Kingdom. WRJT was part supported by France Expertise International through the 5 % initiative as a consultant to CNM in operational research and he expresses 'ses remerciements profonds au peuple français.' JKB is supported by Wellcome Trust grant B9RJIXO. DM is supported the French Ministry of Foreign Affairs and SKim was part funded by a grant from the Asia Pacific Malaria Elimination Network. None of the funders had any role in study design, data collection, analysis, and interpretation, or writing of the manuscript or in the decision to submit the manuscript for publication., and We wish to express our sincere and profound thanks to the patients who took part in this study and to the nurses and laboratory staff who contributed to its successful and safe execution. We thank our DSMB who reviewed the G6PDd data in real time and provided very valuable and timely responses and advice: Drs Toby Leslie (Chairperson), Chanthap Lon, Isabella Ribeiro and Professor Lucio Luzzatto.