Large-scale genetic study identifies targets that could reduce cardiovascular risk by modulating blood metabolites

Graphical abstract of the performed analyses and main results. GWAS: Genome-wide association study. TWAS: Transcriptome-wide association study. MR: Mendelian randomization. Credit: Genome Medicine (2024). DOI: 10.1186/s13073-024-01397-2

A team of researchers have worked together to identify possible genes associated with certain metabolites molecules involved in the body’s biochemical processes and cardiovascular risk.

The scientists analyzed 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-analyzed 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.

 

By Germans Trias i Pujol Research Institute

Article can be accessed on: MedicalXpress