Genome-wide association studies (GWAS) for complex traits, including glycaemia, type 2 diabetes (T2D) and coronary heart disease (CHD) have been successful in identifying genetic variants associated with those phenotypes. However, they explained only a small proportion of the estimated heritability. Possible reasons include the interplay between genetics and lifestyle determinants, small-effect variants, structural variations and the difficult to characterize non-coding functional variants that interact with other genetic regions. This proposal, in a new era of precision medicine, englobes the systematic study of the interplay between genetic variants associated with glycaemia, T2D, CHD and dietary and lifestyle factors. We propose to conduct a comprehensive analysis of gene and gene-lifestyle interaction, including the existing international GWAS consortia of CARDIoGRAM, DIAGRAM, MAGIC, the U.S. based DPP clinical trial, and the European-wide networks of EPIC-InterAct and PREDIMED. We will test hypothesis about: 1) whether genetically driven hyperglycaemia increases risk of CHD, 2) the association between genetic determinants of CHD and intermediate metabolic phenotypes, and 3) whether dietary components and lifestyle changes influence these associations. Finally, we will extend and replicate these previous results in two independent populations, and to deploy a new method to identify implicated biological pathways. Information that will emerge from that project will provide valuable insights into missing heritability for T2D and CHD. Specifically we expect to uncover genetic determinants for faster CHD progression in T2D, identifying vulnerable individuals who are more likely to experience a differential response to current prevention strategies and to validate potential targets and avenues for intervention. The experienced researcher will emerged from the project with new skills, and the capability to launch his own research group in Europe.

EQUAL-LIFE will develop and test combined exposure data using a novel approach to multi-modal exposures and their impact on children’s mental health and development. A combination of birth-cohort data with new sources of data, will provide insight into aspects of physical and social exposures hitherto untapped. It will do this at different scale levels and timeframes, while accounting for the distribution of exposures in social groups based on gender, ethnicity, social vulnerability. Beginning with child development and mental health, a set of theory-based questions is formulated, a wide range of relevant environmental and social hazards is defined and validated at the stakeholders end. Exposure assessment combines traditional GIS-based approaches with omics approaches and new sources of data that could explain aspects of the urban environment at a higher spatial and temporal granularity, and provide insight into untapped parameters relating to exposure (spatial quality of neighborhoods). These together form the early-life exposome. Statistical tools integrate data at different scale levels and times and combine e.g. machine learning, causal models with subgroups measures. EQUAL-LIFE uses data from birth-cohorts, longitudinal school data sets and cross-sectional studies (N=>250.000), including data on exposures, biomarkers, mental health and developmental outcomes, in their social context. EQUAL-LIFE contributes to the development/utilization of the exposome concept by 1) integrating the internal, external and social exposome 2) by studying a distinct set of effects on a child’s development and mental health 3) by characterizing/measuring/modelling the child’s environment at different stages and activity spaces 4) by looking at supportive environments for child development, rather than merely pollutants 5) by combining physical, social indicators with novel biomarkers and using new data sources describing child activity patterns and environments. EQUAL-LIFE is part of the European Human Exposome Network comprised of nine projects selected from this same call.

Tobacco smoking is the leading cause of preventable disease worldwide. Compared with the rest of the world, the WHO European region has one of the highest proportions of deaths attributable to tobacco. Although most of EU countries have introduced smoking bans in public places, domestic environments are still an important source of passive smoking exposure. Environmental tobacco smoke contains more than 4,000 chemicals many of which are toxic and carcinogenic and is estimated to be the cause of about 1.0% of worldwide mortality. In addition to passive inhalation, non-smokers, especially children, are also at risk through contact with surfaces and dust contaminated with residual smoke gases and particles, the so-called thirdhand tobacco smoke (THS). Despite the emerging evidence on THS harms, the specific role of THS in tobacco-related illnesses has been questioned so far by the public health community because of the poor level of characterisation of THS constituents and mechanisms of formation, as well as the lack of studies focused on human exposure. The aim of this proposal is to fill some of the important gaps on our current understanding of the chemistry, toxicology and exposure of THS, including an accurate characterisation of THS composition and the development and validation of specific human urine biomarkers of this exposure. The developed tools will be used for the monitoring of matching samples of THS from smoking and non-smoking houses and human urine from their households in order to find correlations between tobacco exposure and urine biomarkers. The final objective of the proposal is the public diffusion of the results obtained in this study as evidences of THS harms to influence in present and future health educational programs, especially addressed to smoking parents, and in present and future European health policies.

Colorectal cancer (CRC) is the most common neoplastic pathology in the developed world. It is the second in frequency in men after prostate cancer and the second in women after breast cancer. Survival at five years, if all stages are taken into account, is approximately 50%. That represents a mortality of 20 cases per 100,000 inhabitants per year. The five-year survival of early stages, a situation almost equivalent to cure, is approximately 90%, whereas in advanced or metastatic stages it is less than 10%. Therefore, early diagnosis plays a central role in the improvement of survival rates. The main goal of this project is to find new ways to detect the cancer in the very early stages. To do so, the sample collection must be as simple, economic and convenient as possible. Only in this manner, regular screening approaching 100% of adult population will take place. The approach we propose is the identification and validation of new biomarkers in urine that can be used to diagnose colorectal cancer (CRC) at a very early stage. The central hypothesis is that CRC associated metabolites in the urine of patients can be segregated from patients with polyps (some of them precursors of CRC) and control subjects, and that their levels are correlated with clinical diagnostics of a CRC stage. Urine is an easy collectible biofluid for its non-invasiveness, and it can provide early detection of cancers. New sample measurement protocols and techniques are enhancing both selectivity and sensitivity by orders of magnitude, such as SPME and Twisters or GC/LC-MS systems (GCxGX/LC-QTOF-MS). The more sensitivity and selectivity, the more confindent diagnosis could be made at earlier stages of the cancerous process leading to a better survivability rate. Moreover, our proposal includes a multi-cohort, multi-laboratory validation of the findings, therefore ensuring that any discovery can readily be applied to any population and instrumentation around de world.

Work environments are rapidly changing in Europe. The COVID-19 pandemic resulted in an acceleration of a range of complex and multidimensional trends at the workplace. There is also increasing awareness of the importance of mental and physical health of workers and fundamental interconnections of work, health and well-being. Climate change is further shaping the future of work on an unprecedented scale. European economies are undergoing transformation and reorientation towards sustainability. The European Green Deal is reforming the workplace through implementation of new sustainable work practices and policies, circular economy solutions, and rapid expansion of work in green jobs, resulting in novel workplace exposures with likely impacts on health. Increases in complex algorithmic management and performance monitoring are also taking place with a view towards sustainability. There have been calls towards inclusive green economies ensuring social protection, and the creation of decent green jobs. The overall objective of the INTERCAMBIO project is to promote mental and physical health of workers in changing work environments due to climate change, implementation of new working practices, and among workers in green jobs. We will examine key research questions regarding mental and physical health of workers and conduct detailed evaluation of interventions in strategic industries in Europe relevant to green and digital transitions, including in outdoor construction, health care, public transit, renewable energy (wind turbine), and waste management/recycling using a variety of multidisciplinary and state-of-the-art research methods. We will leverage large, geographically diverse longitudinal cohort consortia for new climate-related studies, promote a framework for social protection, and engage multi-level stakeholders. Findings are expected to have major scientific and societal relevance and will provide support for new policy action in occupational health.