Table 1 |.
Non-malignant conditions associated with clonal haematopoiesis of indeterminate potential
| Diagnosis | Patient cohorts | Odds ratio | Mouse models | In vivo mouse phenotypes | Refs. |
|---|---|---|---|---|---|
| Alzheimer disease | TOPMed, ADSP | ~0.5–0.8 | NA | NA | 117 |
| Atherosclerotic cardiovascular disease | TOPMed, UKB | ~1.1–1.5 |
Tet2–/– bone marrow → Ldlr
–/–mice fed a high fat diet (myeloid-restricted Tet2–/–sufficient mice) |
↑plaque size; ↑IL-1β, CXCL1, CXCL2, CXCL3 | 76,81,82,84,97,129 |
| Atrial fibrillation | UKB | ~1.1–1.2 | NA | NA | 83 |
| Heart failure | TOPMed, UKB | ~1.1–1.5 |
Tet2–/– bone marrow → wild-type mice with subsequent vascular ligation or constriction Tet2 or Dnmt3a CRISPR-Cas9 edited bone marrow → wild-type mice treated with angiotensin II (myeloid-restricted Tet2–/–sufficient mice) |
↑systolic dysfunction; ↓ejection fraction; ↑fibrosis; ↑IL-1β, CCL2, CCL5 | 99,100 |
| Cerebrovascular accidents | TOPMed, UKB, MGBB | ~1.1–1.2 | NA | NA | 116 |
| Chronic kidney disease | UKB | ~1.1–1.5 | Tet2 or Dnmt3a CRISPR-Cas9 edited bone marrow → wild-type mice treated with angiotensin II | ↑fibrosis | 101,102 |
| Chronic liver disease | FHS, ARIC, UKB, MGBB | ~2–4 |
Tet2–/– or Dnmt3a–/– bone marrow → Ldlr
–/– mice fed a high fat diet (myeloid-restricted Tet2–/– sufficient mice) |
↑steatohepatitis; ↑fibrosis; ↑IL-6, CXCL1, CCL22 | 103 |
| Chronic obstructive pulmonary disease | TOPMed, ICGN, EOCOPD, UKB | ~1.5–2 | Tet2–/– bone marrow → wild-type mice exposed to cigarette smoke and poly(I:C) | ↑emphysema; ↑IFNγ and type I IFNs | 104 |
| Gout | UKB, MGBB | ~1.2–1.7 |
Tet2–/– bone marrow → wild-type mice injected with monosodium urate crystals in the footpad |
↑paw oedema; ↑IL-1β, CCL5, CCL22 | 105 |
| Osteoporosis | UKB | ~1.2–1.5 |
Tet2–/–, Dnmt3a–/– or Dnmt3a R878H bone marrow → Ldlr–/–mice fed a high fat diet or wild-type aged mice fed a regular diet |
↓bone mass; ↑osteoclasts | 108 |
| Premature menopause | UKB, WHI | ~1.1–1.7 | NA | NA | 109 |
ARIC, Atherosclerosis Risk in Communities; ADSP, Alzheimer’s Disease Sequencing Project; CCL, CC-chemokine ligand; CXCL, CXC-chemokine ligand; EOCOPD, Boston Early-Onset COPD Study; FHS, Framingham Heart Study; ICGN, International COPD Genetics Network; IFN, interferon; MGBB, Mass General Brigham Biobank; NA, not available; TOPMed, Trans-Omics for Precision Medicine program; UKB, UK Biobank; WHI, Women’s Health Initiative.