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      The Human Early-Life Exposome (HELIX): Project Rationale and Design

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      Environmental Health Perspectives
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          Abstract

          Background: Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure–health effect relationships. The “exposome” concept encompasses the totality of exposures from conception onward, complementing the genome.

          Objectives: The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the “early-life exposome.” Here we describe the general design of the project.

          Methods: In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totaling 32,000 mother–child pairs, and biomarkers will be measured in a subset of 1,200 mother–child pairs. Nested repeat-sampling panel studies ( n = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure–response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures.

          Conclusions: HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step toward the life-course exposome.

          Citation: Vrijheid M, Slama R, Robinson O, Chatzi L, Coen M, van den Hazel P, Thomsen C, Wright J, Athersuch TJ, Avellana N, Basagaña X, Brochot C, Bucchini L, Bustamante M, Carracedo A, Casas M, Estivill X, Fairley L, van Gent D, Gonzalez JR, Granum B, Gražulevičienė R, Gutzkow KB, Julvez J, Keun HC, Kogevinas M, McEachan RR, Meltzer HM, Sabidó E, Schwarze PE, Siroux V, Sunyer J, Want EJ, Zeman F, Nieuwenhuijsen MJ. 2014. The Human Early-Life Exposome (HELIX): project rationale and design. Environ Health Perspect 122:535–544;  http://dx.doi.org/10.1289/ehp.1307204

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          Most cited references59

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          Development of NO2 and NOx land use regression models for estimating air pollution exposure in 36 study areas in Europe – The ESCAPE project

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            Integrated pathway-level analysis of transcriptomics and metabolomics data with IMPaLA.

            Pathway-level analysis is a powerful approach enabling interpretation of post-genomic data at a higher level than that of individual biomolecules. Yet, it is currently hard to integrate more than one type of omics data in such an approach. Here, we present a web tool 'IMPaLA' for the joint pathway analysis of transcriptomics or proteomics and metabolomics data. It performs over-representation or enrichment analysis with user-specified lists of metabolites and genes using over 3000 pre-annotated pathways from 11 databases. As a result, pathways can be identified that may be disregulated on the transcriptional level, the metabolic level or both. Evidence of pathway disregulation is combined, allowing for the identification of additional pathways with changed activity that would not be highlighted when analysis is applied to any of the functional levels alone. The tool has been implemented both as an interactive website and as a web service to allow a programming interface. The web interface of IMPaLA is available at http://impala.molgen.mpg.de. A web services programming interface is provided at http://impala.molgen.mpg.de/wsdoc. kamburov@molgen.mpg.de; r.cavill@imperial.ac.uk; h.keun@imperial.ac.uk Supplementary data are available at Bioinformatics online.
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              Implications of the exposome for exposure science.

              During the 1920s, the forerunners of exposure science collaborated with health professionals to investigate the causes of occupational diseases. With the birth of U.S. regulatory agencies in the 1970s, interest in the environmental origins of human diseases waned, and exposure scientists focused instead upon levels of selected contaminants in air and water. In fact, toxic chemicals enter the body not only from exogenous sources (air, water, diet, drugs, and radiation) but also from endogenous processes, including inflammation, lipid peroxidation, oxidative stress, existing diseases, infections, and gut flora. Thus, even though current evidence suggests that non-genetic factors contribute about 90% of the risks of chronic diseases, we have not explored the vast majority of human exposures that might initiate disease processes. The concept of the exposome, representing the totality of exposures received by a person during life, encompasses all sources of toxicants and, therefore, offers scientists an agnostic approach for investigating the environmental causes of chronic diseases. In this context, it is appropriate to regard the "environment" as the body's internal chemical environment and to define "exposures" as levels of biologically active chemicals in this internal environment. To explore the exposome, it makes sense to employ a top-down approach based upon biomonitoring (e.g. blood sampling) rather than a bottom-up approach that samples air, water, food, and so on. Because sources and levels of exposure change over time, exposomes can be constructed by analyzing toxicants in blood specimens obtained during critical stages of life. Initial investigations could use archived blood from prospective cohort studies to measure important classes of toxic chemicals, notably, reactive electrophiles, metals, metabolic products, hormone-like substances, and persistent organic compounds. The exposome offers health scientists an avenue for integrating research that is currently fractured along lines related to particular diseases and risk factors, and can thereby promote discovery of the key exposures responsible for chronic diseases. By embracing the exposome as its operational paradigm, exposure science can play a major role in discovering and mitigating these exposures.
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                Author and article information

                Journal
                Environ Health Perspect
                Environ. Health Perspect
                EHP
                Environmental Health Perspectives
                NLM-Export
                0091-6765
                1552-9924
                07 March 2014
                June 2014
                : 122
                : 6
                : 535-544
                Affiliations
                [1 ]Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
                [2 ]Universitat Pompeu Fabra (UPF), Barcelona, Spain
                [3 ]CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain
                [4 ]Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Albert Bonniot (U823), Grenoble, France
                [5 ]University of Crete (UOC), Heraklion, Crete, Greece
                [6 ]Imperial College London (ICL), London, United Kingdom
                [7 ]Veiligheids- en Gezondheidsregio Gelderland Midden (VGGM), Arnhem, the Netherlands
                [8 ]Norwegian Institute of Public Health (NIPH), Oslo, Norway
                [9 ]Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust (BTHFT), Bradford, United Kingdom
                [10 ]Sensing & Control Systems S.L. (S&C), Barcelona, Spain
                [11 ]Institut National de l’Environnement Industriel et des Risques (INERIS), Unit of Models for Ecotoxicology and Toxicology, Paris, France
                [12 ]Hylobates Consulting S.R.L. (HYLO), Rome, Italy
                [13 ]Centre for Genomic Regulation (CRG), Barcelona, Spain
                [14 ]IMIM Hospital del Mar Research Insititute, Barcelona, Spain
                [15 ]Grupo de Medicina Xenomica, Fundación Pública Galega de Medicina Xeómica (SERGAS), CIBERER-CEGEN, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
                [16 ]Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia
                [17 ]Vytauto Didziojo Universitetas (VDU), Kaunus, Lithuania
                Author notes
                Address correspondence to M. Vrijheid, Center for Research in Environmental Epidemiology (CREAL), Parc de Recerca Biomèdica de Barcelona–PRBB, C. Doctor Aiguader, 88, 08003 Barcelona, Spain. Telephone: 34 932 147 346. E-mail: mvrijheid@ 123456creal.cat
                Article
                ehp.1307204
                10.1289/ehp.1307204
                4048258
                24610234
                d90a9972-483e-4e9c-838d-4a96fab556a3

                Publication of EHP lies in the public domain and is therefore without copyright. All text from EHP may be reprinted freely. Use of materials published in EHP should be acknowledged (for example, “Reproduced with permission from Environmental Health Perspectives”); pertinent reference information should be provided for the article from which the material was reproduced. Articles from EHP, especially the News section, may contain photographs or illustrations copyrighted by other commercial organizations or individuals that may not be used without obtaining prior approval from the holder of the copyright.

                History
                : 11 June 2013
                : 06 March 2014
                : 07 March 2014
                : 01 June 2014
                Categories
                Review

                Public health
                Public health

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