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Clonal Hematopoiesis Is Associated With Higher Risk of Stroke.

TitleClonal Hematopoiesis Is Associated With Higher Risk of Stroke.
Publication TypeJournal Article
Year of Publication2022
AuthorsBhattacharya R, Zekavat SM, Haessler J, Fornage M, Raffield L, Uddin MMesbah, 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 JAE, Whitsel EA, Natarajan P, Reiner AP
Corporate AuthorsNHLBI Trans-Omics for Precision Medicine Program
JournalStroke
Volume53
Issue3
Pagination788-797
Date Published2022 03
ISSN1524-4628
KeywordsAdult, Aged, Aged, 80 and over, Clonal Hematopoiesis, Dioxygenases, DNA Methyltransferase 3A, DNA-Binding Proteins, Female, Hemorrhagic Stroke, Humans, Incidence, Ischemic Stroke, Male, Middle Aged, Prevalence, Repressor Proteins, Risk
Abstract

BACKGROUND AND PURPOSE: 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.

METHODS: 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 (, , and ) with any stroke, ischemic stroke, and hemorrhagic stroke.

RESULTS: CHIP was associated with an increased risk of total stroke (hazard ratio, 1.14 [95% CI, 1.03-1.27]; =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]; =0.04) and with small vessel ischemic stroke subtypes. In gene-specific association results, showed the strongest association with total stroke and ischemic stroke, whereas and were each associated with increased risk of hemorrhagic stroke.

CONCLUSIONS: 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.

DOI10.1161/STROKEAHA.121.037388
Alternate JournalStroke
PubMed ID34743536
PubMed Central IDPMC8885769
Grant ListR01 AG066134 / AG / NIA NIH HHS / United States
R01 HL143295 / HL / NHLBI NIH HHS / United States
RC2 HL102419 / HL / NHLBI NIH HHS / United States
75N92020D00002 / HL / NHLBI NIH HHS / United States
HHSN268201100001I / HL / NHLBI NIH HHS / United States
F30 HL149180 / HL / NHLBI NIH HHS / United States
UH3 NS100605 / NS / NINDS NIH HHS / United States
75N92021D00002 / HL / NHLBI NIH HHS / United States
HHSN268201500003C / HL / NHLBI NIH HHS / United States
HHSN268201800012I / HB / NHLBI NIH HHS / United States
HHSN268201800012C / HL / NHLBI NIH HHS / United States
R01 NS017950 / NS / NINDS NIH HHS / United States
75N92020D00005 / HL / NHLBI NIH HHS / United States
R01 AT011729 / AT / NCCIH NIH HHS / United States
N01HC95160 / HL / NHLBI NIH HHS / United States
DP5 OD029586 / OD / NIH HHS / United States
R01 AG054076 / AG / NIA NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
75N92021D00005 / WH / WHI NIH HHS / United States
RF1 AG059421 / AG / NIA NIH HHS / United States
R01 HL151283 / HL / NHLBI NIH HHS / United States
N01HC95163 / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
UL1 TR001079 / TR / NCATS NIH HHS / United States
HHSN268201800014I / HB / NHLBI NIH HHS / United States
HHSN271201700002C / DA / NIDA NIH HHS / United States
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HHSN268200800007C / HL / NHLBI NIH HHS / United States
75N92020D00001 / HL / NHLBI NIH HHS / United States
N01HC95169 / HL / NHLBI NIH HHS / United States
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HHSN268201700001C / HL / NHLBI NIH HHS / United States
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HHSN268201700003C / HL / NHLBI NIH HHS / United States
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UH2 NS100605 / NS / NINDS NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
75N92019D00031 / HL / NHLBI NIH HHS / United States
HHSN268201700004C / HL / NHLBI NIH HHS / United States
UL1 TR000040 / TR / NCATS NIH HHS / United States
HHSN268201700002I / HL / NHLBI NIH HHS / United States
HHSN268201800010I / HB / NHLBI NIH HHS / United States
UM1 HG008898 / HG / NHGRI NIH HHS / United States
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UL1 TR001881 / TR / NCATS NIH HHS / United States
R01 HL150170 / HL / NHLBI NIH HHS / United States
HHSN268201800011I / HB / NHLBI NIH HHS / United States
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HHSN268201700003I / HL / NHLBI NIH HHS / United States
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HHSN268201100001C / WH / WHI NIH HHS / United States
R01 AG067513 / AG / NIA NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States