Soluble Immune Checkpoint Protein and Lipid Network Associations with All-Cause Mortality Risk: Trans-Omics for Precision Medicine (TOPMed) Program
Rodriguez, A.; Yang, C.; Gan, W.; Karlinsey, K.; Zhou, B.; Rich, S. S. S.; Taylor, K. D.; Guo, X.; Rotter, J. I. I.; Johnson, W. C.; Cornell, E.; Tracy, R. P.; Durda, P.; Gerszten, R. E.; Clish, C. B.; Blackwell, T. W.; Papanicolaou, G. J.; Lin, H.; Raffield, L. M.; Vargas, J. D.; Vasan, R. S.; Manichaikul, A. W.
Show abstract
Adverse cardiovascular events are emerging with the use of immune checkpoint therapies in oncology. Using datasets in the Trans-Omics for Precision Medicine program (Multi-Ethnic Study of Atherosclerosis, Jackson Heart Study [JHS], and Framingham Heart Study), we examined the association of immune checkpoint plasma proteins with each other, their associated protein network with high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), and the association of HDL-C- and LDL-C-associated protein networks with all-cause mortality risk. Plasma levels of LAG3 and HAVCR2 showed statistically significant associations with mortality risk. Colocalization analysis using genome wide-association studies of HDL-C or LDL-C and protein quantitative trait loci from JHS and the Atherosclerosis Risk in Communities identified TFF3 rs60467699 and CD36 rs3211938 variants as significantly colocalized with HDL-C; in contrast, none colocalized with LDL-C. The measurement of plasma LAG3, HAVCR2, and associated proteins plus targeted genotyping may identify patients at increased mortality risk.
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