A research team from IDIBELL, Institut Català d’Oncologia (ICO), Girona Biomedical Research Institute Dr. Josep Trueta (IDIBGI), IRB Barcelona, and Germans Trias i Pujol Research Institute (IGTP) have worked together to identify possible genes associated with certain metabolites – molecules involved in the body’s biochemical processes – and cardiovascular risk. The scientists analysed the levels of 187 such compounds in plasma samples from 4,974 participants in the Catalan GCAT cohort. They integrated this data with other genetic databases from European individuals, reaching a total of 40,000, and re-analysed the data. As a result, they identified 44 genetic regions associated with these metabolites.

To identify how these genetic regions influence metabolites, the findings were combined with gene expression panels from 58 different tissue and cell types. The researchers were able to pinpoint the genes that, through modulation of their expression, are responsible for the levels of these molecules in the body. This same methodology was applied to data from three European studies involving around 700,000 participants, aiming to study the relationship between gene expression and cardiovascular events, such as heart attacks. Finally, the researchers explored the causal relationship between gene expression, metabolite levels, and cardiovascular risk through a genetic mediation analysis.

Thanks to these various analyses, the researchers have identified a potential molecular mechanism by which six genetic loci (genetic regions) are associated with cardiovascular risk through the metabolites they regulate. In this way, this study, published in Genome Medicine, highlights new genetic targets with therapeutic potential, suggest new targets for drug development and deepen our understanding of the underlying mechanisms of cardiovascular risk but also.

Regulating blood metabolite levels by modulating gene expression could offer a new pathway to reduce cardiovascular events in high-risk populations. This research enables the identification of lipids that act as mediators between the expression of certain genes and cardiovascular risk. As such, it describes a chain of risk factors from genetic predisposition to cardiovascular risk, via gene activation and lipid levels in the blood.

The study underscores the importance of large-scale genetic research for identifying new biomarkers and therapeutic strategies. Identifying key genes associated with metabolites and cardiovascular risk offers the potential to develop personalised treatments, enhancing the prevention and treatment of cardiovascular diseases, which remain one of the leading causes of mortality worldwide.

The Bellvitge Biomedical Research Institute (IDIBELL) is a biomedical research center created in 2004. It is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Institute of Health, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.

IDIBELL is a member of the Campus of International Excellence of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centers accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the “HR Excellence in Research” program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Center of the AECC Scientific Foundation (FCAECC).