J7-9400-1

Summary of the project

Environmental pollutants, including selected toxic elements and their species and organic compounds, are among the known causes for neurodevelopmental diseases, the prevalence of which seem to be increasing world‐wide. Sub‐clinical decrements in neuro‐psychological functions are even more common than neurodevelopmental disorders and can play an important role in aetiology of neurological disorders later in life. Response depends strongly on the individual's compensation mechanisms, particularly at low, environmentally relevant exposures, and may include (epi)genetic predisposition and/or human microbiome. A notable increase of intensity of studies related to the variability in susceptibility to neurotoxic effects at low low‐level of exposure to environmental toxicants has been evidenced.

The project builds on the existing cohort of children PHIME (Public Health Impact of long‐term, low‐level mixed element exposure in susceptible population strata to toxic metals, 2000‐2006) in which child neurodevelopment in relation to mercury (Hg) exposure among residents in the Mediterranean coastal regions of Italy, Slovenia, Croatia and Greece was assessed. The results of the neurodevelopment performance at the 18 months have shown that higher fish consumption during pregnancy was associated with cognitive and language (but not motor) neurodevelopment performance.The subset of children from this cohort were further assessed at 6 to 8 years of age in three countries Slovenia, Croatia and Italy as part of the Life+CHROME project. As a rational approach, this project aims to further exploit the available data and fill data gaps by additional chemical, biochemical and molecular analysis. The main goal of this project is to establish associations between environmental exposure, human (epi)genome and neuropsychological performance, taking into account for the first time also the role of microbiome. As the birth cohorts in three countries followed exactly the same study protocol, the formation of unified study cohort is justified and allows for the sufficient stitistical power in data analyses and interpretation. Moreover, this project is timely as it coincides with the recruitment of a new cohort in Slovenia and Croatia as part of the EU EXHES/HEALS project. This will allow further validation of the study outcomes using methodology built on the validated approach and data.

Strong and committed interdisciplinary institutional arrangements is composed of partners in Slovenia (Jožef Stefan Institute, University Clinical Center Ljubljana) with the expertise covering chemical and biochemical analytical work, pharmacokinetic modelling, experience in recruitment and neurodevelopment testing, bioinformatics and most advanced machine learning techniques ultimately needed for data interpretation and exploitation. The international partners will contribute the data needed for inclusion of Croatian and Italian cohort (University Medical center in Rijeka and Burlo Garofolo. Trieste) as well as classical biostatistical tools. The contribution from Swedish partners, namely Karolinska Institute, Stockholm and Chalmers University, will contribute expertise in advanced genotyping and epigenetic analysis and microbiome, respectively.

Finally, the project will disseminate the results to the science community through an ambitios publication plan, while strong engagement of early stage researchers will create opportunities for their enhanced career prospects in this perspective interdisciplinary science domain. Communication of the study results to different health and environmental sectors at national and international level will also improve the understanding and the use of the complex gene‐environment interactions in chemical management actions. The empowerment of citizens through their active participation (recruited subjects) as well outreach activities will also be an integral part of the project implementation plan.

Participating research institutions

Jožef Stefan Institute

-        Department of Environmental Sciences

-        Department of knowledge technologies

-        Department of Molecular and Biomedical Sciences

Univerzitetni klinični center Ljubljana

Collaborating parties/Partners from the EU or/and from abroad

Burlo Garofolo, Trieste, Italy

University Medical Centre, Rijeka, Croatia

Karolinska Institutet, Stockholm, Sweden

Chalmers University, Bioinformatics and Computational Biology, Goteborg, Sweden

Work packages: