Convergence of coronary artery disease genes onto endothelial cell programs. (https://pubmed.ncbi.nlm.nih.gov/38326615/)

These scientists wanted to understand how certain genes in our bodies can cause diseases like coronary artery disease (CAD). They knew that studying the genes alone is not enough, so they came up with a new method to connect the genes to the functions they perform in our bodies.

First, they looked at a lot of data from previous studies called genome-wide association studies (GWAS). These studies look at many different genes and try to find links between certain gene variations and diseases. But it's not always easy to figure out how these genes actually cause the diseases.

So, the scientists used a special kind of data called epigenomics data. This data tells us how genes are turned on or off in different parts of our bodies. By comparing the GWAS data with the epigenomics data, they were able to link certain gene variations to specific genes in our bodies.

Next, they used a technique called Perturb-seq to figure out which pathways these genes are a part of. A pathway is like a road that genes take to do their jobs. By knowing which genes are in the same pathway, we can understand how they work together to cause diseases.

In this study, the scientists focused on a disease called coronary artery disease (CAD) and a type of cell called endothelial cells. They found that 43 gene variations that are linked to CAD all converge on a pathway called the cerebral cavernous malformation (CCM) signaling pathway.

They also discovered two genes, CCM2 and TLNRD1, that are part of this pathway and are linked to CAD risk. These genes not only affect other genes related to CAD, but they also play a role in protecting our blood vessels from getting clogged.

This study showed that CAD is caused, in part, by the convergence of certain genes onto the CCM signaling pathway in endothelial cells. It also highlighted that there are shared genes between CAD and another disease called cerebral cavernous malformation (CCM).

The scientists also found a new gene, TLNRD1, that was previously not known to be part of the CCM signaling pathway. This means they discovered something new about how this pathway works.

This new method that the scientists used can be used to study other diseases too. It helps us connect gene variations to the functions they perform in our bodies, which is important for understanding and treating diseases.

Schnitzler GR., Kang H., Fang S., Angom RS., Lee-Kim VS., Ma XR., Zhou R., Zeng T., Guo K., Taylor MS., Vellarikkal SK., Barry AE., Sias-Garcia O., Bloemendal A., Munson G., Guckelberger P., Nguyen TH., Bergman DT., Hinshaw S., Cheng N., Cleary B., Aragam K., Lander ES., Finucane HK., Mukhopadhyay D., Gupta RM., Engreitz JM. Convergence of coronary artery disease genes onto endothelial cell programs. Nature. 2024 Feb 7. doi: 10.1038/s41586-024-07022-x.