| Title: | Clonal Hematopoiesis Is Associated With Higher Risk of Stroke |
| Journal: | Stroke |
| Published: | 8 Nov 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34743536/ |
| DOI: | https://doi.org/10.1161/strokeaha.121.037388 |
| URL: | https://www.ahajournals.org/doi/pdf/10.1161/STROKEAHA.121.037388 |
Publication 18687
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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.</p>
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 (DNMT3A, TET2, and ASXL1) with any stroke, ischemic stroke, and hemorrhagic stroke.</p>
RESULTS: 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.</p>
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.</p>
17 Keywords
- Adult
- Aged
- Aged, 80 and over
- Clonal Hematopoiesis
- DNA Methyltransferase 3A
- DNA-Binding Proteins
- Dioxygenases
- Female
- Hemorrhagic Stroke
- Humans
- Incidence
- Ischemic Stroke
- Male
- Middle Aged
- Prevalence
- Repressor Proteins
- Risk
33 Authors
- Romit Bhattacharya
- Seyedeh M. Zekavat
- Jeffrey Haessler
- Myriam Fornage
- Laura Raffield
- Mesbah Uddin
- Alexander G. Bick
- Abhishek Niroula
- Bing Yu
- Christopher Gibson
- Gabriel Griffin
- Alanna C. Morrison
- Bruce M. Psaty
- William T. Longstreth
- Joshua C. Bis
- Stephen S. Rich
- Jerome I. Rotter
- Russell P. Tracy
- Adolfo Correa
- Sudha Seshadri
- Andrew Johnson
- Jason M. Collins
- Kathleen M. Hayden
- Tracy E. Madsen
- Christie M. Ballantyne
- Siddhartha Jaiswal
- Benjamin L. Ebert
- Charles Kooperberg
- JoAnn E. Manson
- Eric A. Whitsel
- NHLBI Trans-Omics for Precision Medicine Program
- Pradeep Natarajan
- Alexander P. Reiner
1 Application
| Application ID | Title |
|---|---|
| 7089 | Exome Sequencing of All Premature Coronary Artery Disease Participants in UK Biobank |
Enabling scientific discoveries that improve human health