Community Research and Development Information Service - CORDIS

FP7

HEALS Report Summary

Project ID: 603946
Funded under: FP7-ENVIRONMENT
Country: France

Periodic Report Summary 2 - HEALS (Health and Environment-wide Associations based on Large population Surveys)

Project Context and Objectives:
We recall here briefly the main features of the HEALS (Health and Environment-wide Associations based on Large Population Surveys) project context and objectives that have been presented elsewhere more extensively.
Explaining and predicting chronic health outcomes implies that the individual environmental exposures, biomarkers of exposure and effect, internal body processes and signals, genetic variations and epigenetic marks are reliably measured simultaneously during his/her entire lifespan. This entails the introduction of the notion of the exposome, i.e. the totality of exposures from preconception onwards, simultaneously identifying, characterizing and quantifying the exogenous and endogenous exposures and hence modifiable risk factors that predispose to and predict diseases throughout a person’s lifespan. The HEALS project brings together in an innovative approach a comprehensive array of novel technologies, data analysis and modeling tools that support efficiently exposome estimation and exposome-wide association studies to improve health risk assessment of environmental stressors.

The general objective of HEALS is the refinement of an integrated methodology and the application of the corresponding analytical and computational tools to real-life population samples for performing environment (or exposome)-wide association studies (EWAS) in support of EU-wide environment and health risk assessments. This constitutes the HEALS paradigm.

In the HEALS project, EWAS is applied on three classes of health outcomes - asthma and allergies, childhood obesity and type 2 diabetes, neurodevelopmental and neurodegenerative disorders, the prevalence of which is elevated (and is continuously increasing) in the European population, even at early life. These outcomes are deemed to be interrelated to each other and to share common risk factors, as well as common toxicity pathway nodes.
More in detail, the HEALS approach intends to harmonize environmental, socio-economic, exposure and effect biomarkers and health data on different levels (from ecological to individual) and to collate processes and computational pipelines that are necessary for comprehensive environmental exposure-health associations explaining the development of the considered health outcomes.
The overall HEALS approach is verified and refined in a series of pre-existing population studies across Europe including singletons and twin cohorts and registries, accounting for different class of ages, levels of environmental exposure, windows of exposure, socio-economics, biomarkers of exposure and effects and epi/genetic variability, with focus on the above-mentioned health outcomes. It is applied on a pilot environmental EXposure and Health Examination Survey (EXHES) of children including sets of singletons and of twins with matched singletons (each twin pair having also a matched singleton) and their parents covering ten EU Member States.
To attain its objectives, the HEALS project has been structured in 7 streams and 20 work-packages (WPS). And this work organisation has been effective with most of the objectives and technical goals of the period 19 – 36 months achieved. Six streams are still active.
For the second period of work, the specific objectives comprised:
1) the implementation of the HEALS exposure biology workflow to unravel the internal exposome
2) the estimation of the external exposome using integrated exposure assessment methods coupling near- and far-field exposure monitoring and modeling
3) and as a permanent objective, the continuation of reporting, networking, disseminating and training at the national and international level.

More up-to-date information on HEALS can be found at the project public website http://www.heals-eu.eu/.

Project Results:
The HEALS project has advanced importantly in the second period through the implementation of novel methodologies to decipher the internal and the external exposome paving the way for EWAS in order to capture the contribution of the environment in the development of the main health outcome phenotypes considered in the project. The main results achieved thus far comprise the creation of unique databases of exposures and health at the European level, the development and implementation of algorithms, models, tools for the reconstruction of the European population exposome, and the investigation of the links between the exposome and the considered health outcomes.
The obtained achievements are:
Health data:
A harmonized database containing datasets on symptoms, diseases, phenotypes from pre-existing studies of singletons and twins is presently available. So far it contains records for more than 50,000 individuals, most followed-up in time, some since birth and even in utero life. Almost half are twins, which will allow investigating the proper role of environment and epigenetic marks in twins sharing the same genetic background. This dataset is presently expanding to accommodate health data from other datasets.
Internal exposome:
Biomarkers of exposure and effects were compiled in various datasets including omics and models. Omics have been employed on samples available from existing exposure/disease outcome studies. Progress was made towards the completion of the major objectives in terms of biokinetic modeling for internal dose and exposure reconstruction. The generic multi-route lifetime PBBK model which includes gestation and breastfeeding and incorporates in utero exposure and mixtures interactions was completed and validated. The development of the modeling framework for human biomonitoring data assimilation by linking biomarker data to exposure burden from multiple routes has been also fully implemented. Work has been done in the association between human biomonitoring data and Biologically Effective Dose using population cohort data relevant to HEALS (REPRO-PL and HERACLES). In addition, information from other existing initiatives on omics was collected and links to other omics databases were made accessible.
External exposome:
Two harmonized databases were built: one containing risk (environmental) factors from pre-existing population-based studies of singletons and twins (individual or semi-individual level), and a second one containing exposure data available on the European level (ecological level). A considerable large number of environmental data sets including food contamination have been identified, collected and analysed for their quality (assessing their QA/QC procedures). Besides environmental factors assessed at the various levels ranging from the ecological to the individual, a probabilistic exposure-modelling framework to assess external exposure to chemicals for selected population groups was established. Data on non-specific environment (socio-economic, community characteristics, health care system, etc.) were also modelled and collected and used to model individual external exposure following time activity patterns for people in different SES sub-groups through Agent-Based Modeling. These models allowed us to estimate lifespan exposure to multiple stressors. The HEALS Environmental Data Management System (EDMS) was implemented to pull together the available environmental data at the European level and more specifically in the cities from which are drawn the pre-existing study populations, the cities participating at the sensors pilot (WP9) and EXHES (WP17).

All the health and environment datasets of observed and modelled data include the spatio-temporal dimension and are going to be gathered in the HEALS platform (GeoDatabase), a unique tool for the investigation of exposome. To date, no database containing ecological and individual, observed or modelled health data, specific and non-specific environmental factors, internal exposome data as a function of the space and the time since 1970 and related weblinks and literature exists in Europe.

Additional results
Among other major milestones of the project achieved in the 2nd reporting period are the following:
• Review of the recent literature about exposure and health association studies, and about biomarkers of exposure and their effects on health outcomes under study in HEALS has been conducted (asthma and allergy, neurodevelopmental and neurodegenerative problems and metabolic disorders, namely obesity and type 2 diabetes).
• Revision of the statistical methods to be applied in EWAS has progressed. In terms of the internal exposome, suitable data mining techniques for biomarker identification and methods for EWAS were finalized in view of processing mixed data from various sources. Definition of the methodological developments for taking into account the socio-economic status of the studied population in the exposome approach was also finalized. Using the results from a task force and further literature searches, we were able to create preliminary ‘rules’ for our Agent Based Modeling (ABM).
• A pilot study testing the reliability of remote and personal sensors for monitoring exposure at the individual level was conducted in 5 countries. It provided recommendations for the EXposure and Health Examination Survey (EXHES) field campaign.
• EXHES has started in 3 countries and will start soon in the remaining 7.
• Regarding the rest of activities, training and dissemination activities: reporting, meeting, networking and disseminating towards scientists but also stakeholders were continued intensely.
• In addition, the key training tools developed in the project are available in the project web-based training portal (HEALS Moodle platform).

Potential Impact:
HEALS findings will be employed to understand the onset and development of multifactorial diseases that demand both genetic and environmental exposures to occur and assess the respective health risk to the European population. More in general, the lessons learned from HEALS will be translated into scientific advice towards the development of protocols and guidelines for setting up of a larger Europe an environment and health examination survey and enhancing health risk assessment via the operational use of the exposome.

List of Websites:
http://www.heals-eu.eu/

Related information

Reported by

UNIVERSITE PIERRE ET MARIE CURIE - PARIS 6
France
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