Genetic Interleukin 6 Signaling Deficiency Attenuates Cardiovascular Risk in Clonal Hematopoiesis
Authors' conclusion
CHIP is associated with increased risk of incident CVD. Among carriers of large CHIP clones, genetically reduced IL-6 signaling abrogated this risk.
Study context
- Population
- UK Biobank individuals without prevalent cardiovascular disease (CVD)
- Participants
- 35,416 individuals
- Exposure
- Clonal hematopoiesis of indeterminate potential (CHIP) vs no CHIP; modification by IL6R p.Asp358Ala
- CHIPn = 1,079
- Large CHIP clonesn = 432
- Outcome
- Incident CVD events:
- MI
- Coronary revascularization
- Stroke
- Death
- Follow-up
- 6.9-year median
Methodological detailsUK Biobank, exome sequencing
- UK Biobank
- Exome sequencing
Main finding
As reported in the abstract
Incident CVD events
Each group vs no CHIPHazard ratio (95% CI)P value
CHIP
1.27(1.04–1.56)
P = 0.019Large CHIP clones
1.59(1.21–2.09)
P < 0.001IL6R p.Asp358Alaamong large CHIP clones
0.46(0.29–0.73)
P < 0.001IL6R p.Asp358Alawithout CHIP
0.95(0.89–1.01)
P = 0.08Observational data: associations, not effects.
Further findings
MI by CHIP status, modified by IL6R p.Asp358Ala (independent sample, n=9951)
- Association of CHIP with MI similarly varied by IL6R p.Asp358Ala
- P for interaction = 0.036
Original publication
Genetic Interleukin 6 Signaling Deficiency Attenuates Cardiovascular Risk in Clonal Hematopoiesis. Circulation. Published 11 November 2019. doi:10.
Summarised from the published abstract; every number is checked against it