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Bhattacharya R, Zekavat SM, Haessler J, Fornage M, Raffield L, Uddin MM, Bick AG, Niroula A, Yu B, Gibson C, Griffin G, Morrison AC, Psaty BM, Longstreth WT, Bis JC, Rich SS, Rotter JI, Tracy RP, Correa A, Seshadri S, Johnson A, Collins JM, Hayden KM, Madsen TE, Ballantyne CM, Jaiswal S, Ebert BL, Kooperberg C, Manson JE, Whitsel EA, NHLBI Trans-Omics for Precision Medicine Program , Natarajan P, Reiner AP
Stroke 53 (3) 788-797 [2022-03-00; online 2021-11-08]
Clonal hematopoiesis of indeterminate potential (CHIP) is a novel age-related risk factor for cardiovascular disease-related morbidity and mortality. The association of CHIP with risk of incident ischemic stroke was reported previously in an exploratory analysis including a small number of incident stroke cases without replication and lack of stroke subphenotyping. The purpose of this study was to discover whether CHIP is a risk factor for ischemic or hemorrhagic stroke. We utilized plasma genome sequence data of blood DNA to identify CHIP in 78 752 individuals from 8 prospective cohorts and biobanks. We then assessed the association of CHIP and commonly mutated individual CHIP driver genes (DNMT3A, TET2, and ASXL1) with any stroke, ischemic stroke, and hemorrhagic stroke. CHIP was associated with an increased risk of total stroke (hazard ratio, 1.14 [95% CI, 1.03-1.27]; P=0.01) after adjustment for age, sex, and race. We observed associations with CHIP with risk of hemorrhagic stroke (hazard ratio, 1.24 [95% CI, 1.01-1.51]; P=0.04) and with small vessel ischemic stroke subtypes. In gene-specific association results, TET2 showed the strongest association with total stroke and ischemic stroke, whereas DMNT3A and TET2 were each associated with increased risk of hemorrhagic stroke. CHIP is associated with an increased risk of stroke, particularly with hemorrhagic and small vessel ischemic stroke. Future studies clarifying the relationship between CHIP and subtypes of stroke are needed.
PubMed 34743536
DOI 10.1161/STROKEAHA.121.037388
Crossref 10.1161/STROKEAHA.121.037388