AI Article Synopsis
- Coronary artery disease (CAD) is a major global health issue, prompting researchers to seek new treatment targets through advanced genetic analyses.
- The study examined over 20,000 genes and nearly 1,800 plasma proteins, identifying 19 proteins and 119 genes significantly linked to CAD risk using instrumental variable and genetic colocalization methods.
- Among the findings, well-known targets like PCSK9 were validated, while new candidates such as HTRA1 and endotrophin were identified, highlighting the need for further experimental studies to confirm these connections to CAD.
Article Abstract
Coronary artery disease (CAD) remains a leading cause of disease burden globally, and there is a persistent need for new therapeutic targets. Instrumental variable (IV) and genetic colocalization analyses can help identify novel therapeutic targets for human disease by nominating causal genes in genome-wide association study (GWAS) loci. We conducted cis-IV analyses for 20,125 genes and 1,746 plasma proteins with CAD using molecular trait quantitative trait loci variant (QTLs) data from three different studies. 19 proteins and 119 genes were significantly associated with CAD risk by IV analyses and demonstrated evidence of genetic colocalization. Notably, our analyses validated well-established targets such as PCSK9 and ANGPTL4 while also identifying HTRA1 and endotrophin (a cleavage product of COL6A3) as proteins whose levels are causally associated with CAD risk. Further experimental studies are needed to confirm the causal role of the genes and proteins identified through our multiomic cis-IV analyses on human disease.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11233907 | PMC |
| http://dx.doi.org/10.1016/j.isci.2024.110104 | DOI Listing |
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