Challenge

Early-life stress can shape health long after the original experience has passed, increasing the risk of depression, cardiovascular disease and metabolic disorders such as diabetes. However, the biological processes connecting early adversity to these conditions and explaining why they frequently occur together remain insufficiently understood. Differences in sex and gender, socioeconomic circumstances, lifestyle and behaviour add further complexity, making it difficult to identify high-risk individuals and provide timely, coordinated prevention or care.

Solutions

EarlyCause combined evidence from large European population cohorts with animal studies, cellular models and casual-interference methods, such as Mendelian randomisation. Researchers examined four interconnected biological areas: epigenetics, inflamation, the neuroendocrine system and the microbiome, and integrated clinical and multi-omics data using bioinformatics and machine learning. This approach allowed the consortium to investigate possible causal pathways, identify biomarkers and model how multimorbidity develops across the life course.

Results

EarlyCause strengthened the evidence that prenatal and childhood stress is linked to poorer mental and cardiometabolic health. The project identified gene-environment interactions, inflammatory and epigenetic pathways, candidate biomarkers and multi-omics signatures associated with early-life stress. Its genetic analyses highlighted 11 variants and 18 genes, mainly connected to immune and inflammatory processes, while animal studies indicated that environmental enrichment may help reverse some effects of postnatal stress.

Machine-learning analyses identified six distinct multimorbidity trajectories and supported the development of a new assessment tool that performed better than conventional models in predicting cardiovascular disease and diabetes. Together with EarlyCause Data Portal, white papers and socioeconomic assessment framework, these results provide a foundation for improved risk assessment, more targeted prevention and integrated care that considers early-life stress.