Clonal hematopoiesis of indeterminate potential and type 2 diabetes mellitus among patients with STEMI: from a prospective cohort study combing bidirectional Mendelian randomization
Authors' conclusion
CHIP mutations, particularly TET2, are more prevalent in patients with T2DM compared to individuals without diabetes. The presence of these mutations is associated with adverse clinical outcomes, notably increased mortality rates. Moreover, bidirectional Mendelian randomization analyses provide supporting evidence for a potential causal relationship between TET2-related CHIP and the development of T2DM.
Study context
- Population
- Patients with acute MI (STEMI); MR using UK Biobank TET2 CH GWAS (2041 cases, 173,918 controls) and FinnGen T2D (65,085 cases, 335,112 controls)
- Participants
- 1,430 patients
- Exposure
- T2D vs non-DM
- T2Dn = 473
- Non-DMn = 930reference
- Outcome
- Prevalence of CHIP mutations (variant allele fraction ≥ 2.0%) in T2D vs non-DM
Methodological detailsdeep-targeted sequencing with unique molecular identifier (UMI) (42 clonal hematopoiesis of indeterminate potential (CHIP) mutations), two-sample bidirectional Mendelian randomization
- Deep-targeted sequencing with UMI (42 CHIP mutations)
- Two-sample bidirectional Mendelian randomization
Main finding
As reported in the abstract
P < 0.05
Observational data: associations, not effects.
Further findings
Mortality with any CHIP mutation in DM
| aHR (95% CI) | P value | ||
|---|---|---|---|
| Any CHIPMultivariable adjusted | 2.03 (1.07–3.84) | P < 0.05 | |
| 0.20.5125Adjusted hazard ratio (log scale) |
Mortality with TET2 somatic mutation in T2D
| aHR (95% CI) | P value | ||
|---|---|---|---|
| TET2 | 5.24 (2.02–13.61) | P = 0.001 | |
| 0.050.21520Adjusted hazard ratio (log scale) |
Cardiac death with ASXL1 CHIP mutation
| HR (95% CI) | P value | ||
|---|---|---|---|
| ASXL1 | 3.14 (1.24–7.93) | P < 0.05 | |
| ASXL1 (T2DM subgroup) | 4.51 (1.30–15.6) | P < 0.05 | |
| 0.050.21520Hazard ratio (log scale) |
Correlation of PCSK9 with Tet2-CHIP mutation
- T2DM cohort correlation (P = 0.011)
- 0.1215
- Overall cohort correlation (P = 0.0382)
- 0.0578
Bidirectional Mendelian randomization
- Development of T2D increases the propensity for CHIP; CHIP does not accelerate onset of T2D
Original publication
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