Zhi Yu, Trevor P Filder, Yunfeng Ruan, Caitlyn Vlasschaert, Tetsushi Nakao, Md Mesbah Uddin, Taralynn Mack, Abhishek Niroula, J Brett Heimlich, Seyedeh M Zekavat, Christopher J Gibson, Gabriel K Griffin, Yuxuan Wang, Gina M Peloso, Nancy Heard-Costa, Daniel Levy, Ramachandran S Vasan, François Aguet, Kristin G Ardlie, Kent D Taylor, Stephen S Rich, Jerome I Rotter, Peter Libby, Siddhartha Jaiswal, Benjamin L Ebert, Alexander G Bick, Alan R Tall, Pradeep Natarajan
Clonal hematopoiesis of indeterminate potential (CHIP) is associated with an increased risk of cardiovascular diseases (CVD), putatively via inflammasome activation. We pursued an inflammatory gene modifier scan for CHIP-associated CVD risk among 424,651 UK Biobank participants. CHIP was identified using whole exome sequencing data of blood DNA and modeled both as a composite and for common drivers (DNMT3A, TET2, ASXL1, and JAK2) separately. We developed predicted gene expression scores for 26 inflammasome-related genes and assessed how they modify CHIP-associated CVD risk...
July 27, 2023: Journal of Clinical Investigation