Title | Clonal Hematopoiesis Is Associated With Higher Risk of Stroke. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Bhattacharya 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 Authors | NHLBI Trans-Omics for Precision Medicine Program |
Journal | Stroke |
Volume | 53 |
Issue | 3 |
Pagination | 788-797 |
Date Published | 2022 03 |
ISSN | 1524-4628 |
Keywords | Adult, 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. |
DOI | 10.1161/STROKEAHA.121.037388 |
Alternate Journal | Stroke |
PubMed ID | 34743536 |
PubMed Central ID | PMC8885769 |
Grant List | R01 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 T32 GM136651 / GM / NIGMS NIH HHS / United States U01 HL130114 / HL / NHLBI NIH HHS / United States R01 HL146636 / HL / NHLBI NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States 75N92020D00001 / HL / NHLBI NIH HHS / United States N01HC95169 / HL / NHLBI NIH HHS / United States U01 HL120393 / HL / NHLBI NIH HHS / United States R01 HL148565 / HL / NHLBI NIH HHS / United States N01HC95164 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States U54 HG003273 / HG / NHGRI NIH HHS / United States R01 AG049607 / AG / NIA NIH HHS / United States R01 HL142599 / HL / NHLBI NIH HHS / United States HHSN268201800014C / HL / NHLBI NIH HHS / United States N01HC95162 / HL / NHLBI NIH HHS / United States K23 HL140081 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States 75N92020D00003 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States N01HC95168 / HL / NHLBI NIH HHS / United States 75N92021D00001 / HL / NHLBI NIH HHS / United States T32 HL129982 / HL / NHLBI NIH HHS / United States T32 HL007208 / HL / NHLBI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States HHSN268201700002C / HL / NHLBI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States HHSN268201800001C / HL / NHLBI NIH HHS / United States HHSN268201700001I / HL / NHLBI NIH HHS / United States HHSN268201800013I / MD / NIMHD NIH HHS / United States R01 HL143224 / HL / NHLBI NIH HHS / United States HHSN268201700004I / HL / NHLBI NIH HHS / United States N01HC95165 / HL / NHLBI NIH HHS / United States N01HC95159 / HL / NHLBI NIH HHS / United States 75N92021D00003 / WH / WHI NIH HHS / United States R01 AG058969 / AG / NIA NIH HHS / United States R01 HL034594 / HL / NHLBI NIH HHS / United States N01HC95161 / HL / NHLBI NIH HHS / United States R01 NS114045 / NS / NINDS NIH HHS / United States UL1 TR001420 / TR / NCATS NIH HHS / United States 75N92020D00004 / HL / NHLBI NIH HHS / United States R01 HL136574 / HL / NHLBI NIH HHS / United States DP2 HL157540 / HL / NHLBI NIH HHS / United States HHSN268201800011C / HL / NHLBI NIH HHS / United States 75N92020D00007 / HL / NHLBI NIH HHS / United States P30 AG066546 / AG / NIA NIH HHS / United States HHSN268201500003I / HL / NHLBI NIH HHS / United States KL2 TR002490 / TR / NCATS NIH HHS / United States U01 AG052409 / AG / NIA NIH HHS / United States 75N92021D00006 / HL / NHLBI NIH HHS / United States HHSN268201700001C / HL / NHLBI NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States N01HC95167 / HL / NHLBI NIH HHS / United States HHSN268201700003C / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States HHSN268201800015I / HB / NHLBI NIH HHS / United States 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 R01 HL117626 / HL / NHLBI NIH HHS / United States 75N92020D00006 / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01HC95166 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States UL1 TR001881 / TR / NCATS NIH HHS / United States R01 HL150170 / HL / NHLBI NIH HHS / United States HHSN268201800011I / HB / NHLBI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States HHSN268201700003I / HL / NHLBI NIH HHS / United States R01 HL148050 / HL / NHLBI NIH HHS / United States 75N92021D00004 / WH / WHI NIH HHS / United States HHSN268201100001C / WH / WHI NIH HHS / United States R01 AG067513 / AG / NIA NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States |