CHIP Associated Genetic CHD Risk

A Chinese cohort study revealed that clonal hematopoiesis of indeterminate potential (CHIP) contributed to incident coronary heart disease (CHD), and could be modified by germline genetic risk, especially in inflammatory genes. The study used data from 3 prospective cohorts in China.  Participants (n=6181, median age 53.8, female 49.9%) without cardiovascular disease or cancer at baseline were enrolled in 2001 and 2008 with a median follow-up of 12.17 years extending into 2021. A total of 1100 individuals (17.80%) harbored 1372 CHIP mutations at baseline. CHIP was independently associated with incident CHD (hazard ratio [HR], 1.42) and presented a risk gradient with increasing variant allele fraction (VAF). Individuals with small clones, nearly half of CHIP carriers, also demonstrated a higher CHD risk compared with non-CHIP carriers (HR 1.33) and were 4 years younger than those with VAF of 2% or greater (median age, 58.52 vs 62.70 years). Elevated CHD risk was not observed among CHIP carriers with low polygenic risk score (PRS, HR 1.02), while high PRS and CHIP jointly contributed a 2.23-fold increase in risk compared with non-CHIP carriers with low PRS. The diversity in CHIP-related CHD risk within each PRS group was substantially reduced when removing variants in the inflammatory pathway from the PRS. The findings suggest that elevated CHD risk attributed to CHIP was nonnegligible even for small clones. Source: https://jamanetwork.com/