Characteristics and impact of CHIP among individuals without symptomatic cardiovascular disease
| Cohort name . | Recruitment period . | Geographical region . | No. of participants . | Age (mean or median), y . | Ethnicity, race, or ancestry (%) . | Female, % . | Participants with CHIP (VAF of ≥2% unless otherwise specified) . | Most common CHIP loci (% distribution) . | Follow-up duration (y) from genome sequencing . | Impact of CHIP (VAF of ≥2% unless otherwise specified) . | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Coronary artery disease∗ . | Ischemic stroke† . | Peripheral arterial disease . | VTE‡ . | ||||||||||
| UKB20,40-43 | 2006-2010 | United Kingdom | 454 803 (arterial) 425 399 (venous) | Eligibility: 40-69 Overall: 56 (mean) | European: 95 African: 2 South Asian: 2 Other: 0.9 | 54 | 21 137 (4.6%) | DNMT3A: 68.5 TET2: 19.5 ASXL1: 9.0 PPM1D: 3.0 TP53: 1.9 | 13.5 | HR, 1.0; 95% CI, 1.0-1.1; P = .12§ VAF ≥10%: HR, 1.1; 95% CI, 1.0-1.2; P = .004 TET2 CHIP: HR, 1.3; 95% CI, 1.1-1.5 | HR, 1.1; 95% CI, 0.8-1.4|| | HR, 1.6; 95% CI, 1.1-2.3¶, VAF ≥10%: HR, 2.1; 95% CI, 1.4-3.3¶ | VTE overall: HR 1.2; 95% CI, 1.0-1.3; P = .01 VAF ≥10%: HR 1.2; 95% CI, 1.1-1.4 PE: HR, 1.17; 95% CI, 1.1-1.3 VAF ≥10%: HR, 1.2; 95% CI, 1.1-1.4; P = .002 TET2 CHIP: HR, 1.4; 95% CI, 1.2-1.7 |
| Women’s Health Initiative40 | 1993-1998 | United States | 9 683 | Eligibility: 50-79 Overall: 68.9 | White: 82.5 Black: 12.3 Other: 5.2 | 100 | 904 (9.3%) | DNMT3A: 59.1 TET2: 23.5 ASXL1: 7.1 JAK2: 4.3 TP53: 1.8 | 10.8 | NR | Any ischemic stroke: HR, 1.2 (P = .03) Small vessel: HR, 1.6 (P = .001) Large artery: HR, 1.1 (P = .62) Cardioembolic: HR, 1.05 (P = .68) | NR | NR |
| BioImage39 | 2008-2009 | United States | 370 | Eligibility: 55-80 Overall: 70 (median) | European: 100 | 38.3 | 44 (11.9%) | DNMT3A: 31.8 TET2: 15.9 ASXL1: 13.6 | 2.6 | HR, 1.8; 95% CI, 1.1-2.9 | NR | NR | NR |
| Malmo Diet and Cancer39 | 1991-1996 | Malmö, Sweden | 640 | Overall: 60 (median) | NR | 39.0 | 33 (5.1%) | DNMT3A: 45.5 TET2: 18.2 ASXL1: 18.2 | 17.7 | HR, 2.0; 95% CI, 1.2-3.1 | NR | NR | NR |
| China-PAR44 | 1998-2008 | China | 6 181 | Overall: 53.8 | Chinese: 100 | 49.9 | 658 (10.6%) | DNMT3A: 50.0 TET2: 28.0 | 12.2 | VAF 2%-10%: HR, 1.5; 95% CI, 1.1-1.9 VAF ≥10%: HR, 1.8; 95% CI, 1.1-3.1 | NR | NR | NR |
| GESUS45 | January 2010-October 2013 | Naestved, Denmark | 19 958 | Eligibility: ≥30 and 25% of 20-30 | NR | Overall: NR JAK2 V617F CHIP carriers: 46 | 92 (0.5%) with JAK2 V617F ≥1% and no MPN | JAK2 V617F: 100 Allele burden ≥1%: 12. Allele burden ≥10%: 5 | NR | VAF ≥1%: OR, 0.7; 95% CI, 0.2-2.4 | VAF ≥1%: OR, 0.57; 95% CI, 0.14-2.4 | NR | VAF ≥1%: OR, 2.8; 95% CI, 1.1-7.0 |
| Cohort name . | Recruitment period . | Geographical region . | No. of participants . | Age (mean or median), y . | Ethnicity, race, or ancestry (%) . | Female, % . | Participants with CHIP (VAF of ≥2% unless otherwise specified) . | Most common CHIP loci (% distribution) . | Follow-up duration (y) from genome sequencing . | Impact of CHIP (VAF of ≥2% unless otherwise specified) . | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Coronary artery disease∗ . | Ischemic stroke† . | Peripheral arterial disease . | VTE‡ . | ||||||||||
| UKB20,40-43 | 2006-2010 | United Kingdom | 454 803 (arterial) 425 399 (venous) | Eligibility: 40-69 Overall: 56 (mean) | European: 95 African: 2 South Asian: 2 Other: 0.9 | 54 | 21 137 (4.6%) | DNMT3A: 68.5 TET2: 19.5 ASXL1: 9.0 PPM1D: 3.0 TP53: 1.9 | 13.5 | HR, 1.0; 95% CI, 1.0-1.1; P = .12§ VAF ≥10%: HR, 1.1; 95% CI, 1.0-1.2; P = .004 TET2 CHIP: HR, 1.3; 95% CI, 1.1-1.5 | HR, 1.1; 95% CI, 0.8-1.4|| | HR, 1.6; 95% CI, 1.1-2.3¶, VAF ≥10%: HR, 2.1; 95% CI, 1.4-3.3¶ | VTE overall: HR 1.2; 95% CI, 1.0-1.3; P = .01 VAF ≥10%: HR 1.2; 95% CI, 1.1-1.4 PE: HR, 1.17; 95% CI, 1.1-1.3 VAF ≥10%: HR, 1.2; 95% CI, 1.1-1.4; P = .002 TET2 CHIP: HR, 1.4; 95% CI, 1.2-1.7 |
| Women’s Health Initiative40 | 1993-1998 | United States | 9 683 | Eligibility: 50-79 Overall: 68.9 | White: 82.5 Black: 12.3 Other: 5.2 | 100 | 904 (9.3%) | DNMT3A: 59.1 TET2: 23.5 ASXL1: 7.1 JAK2: 4.3 TP53: 1.8 | 10.8 | NR | Any ischemic stroke: HR, 1.2 (P = .03) Small vessel: HR, 1.6 (P = .001) Large artery: HR, 1.1 (P = .62) Cardioembolic: HR, 1.05 (P = .68) | NR | NR |
| BioImage39 | 2008-2009 | United States | 370 | Eligibility: 55-80 Overall: 70 (median) | European: 100 | 38.3 | 44 (11.9%) | DNMT3A: 31.8 TET2: 15.9 ASXL1: 13.6 | 2.6 | HR, 1.8; 95% CI, 1.1-2.9 | NR | NR | NR |
| Malmo Diet and Cancer39 | 1991-1996 | Malmö, Sweden | 640 | Overall: 60 (median) | NR | 39.0 | 33 (5.1%) | DNMT3A: 45.5 TET2: 18.2 ASXL1: 18.2 | 17.7 | HR, 2.0; 95% CI, 1.2-3.1 | NR | NR | NR |
| China-PAR44 | 1998-2008 | China | 6 181 | Overall: 53.8 | Chinese: 100 | 49.9 | 658 (10.6%) | DNMT3A: 50.0 TET2: 28.0 | 12.2 | VAF 2%-10%: HR, 1.5; 95% CI, 1.1-1.9 VAF ≥10%: HR, 1.8; 95% CI, 1.1-3.1 | NR | NR | NR |
| GESUS45 | January 2010-October 2013 | Naestved, Denmark | 19 958 | Eligibility: ≥30 and 25% of 20-30 | NR | Overall: NR JAK2 V617F CHIP carriers: 46 | 92 (0.5%) with JAK2 V617F ≥1% and no MPN | JAK2 V617F: 100 Allele burden ≥1%: 12. Allele burden ≥10%: 5 | NR | VAF ≥1%: OR, 0.7; 95% CI, 0.2-2.4 | VAF ≥1%: OR, 0.57; 95% CI, 0.14-2.4 | NR | VAF ≥1%: OR, 2.8; 95% CI, 1.1-7.0 |
MPN, myeloproliferative neoplasm; NR, not reported.
Adjusted for age, sex, lipid profile, smoking, body mass index, hypertension, and diabetes (or glycemic control) at minimum.
Adjusted for age, sex, smoking status, diabetes, hypertension, and principal components of genetic ancestry at minimum.
Adjusted for age, sex, ethnicity, or principal components of genetic ancestry, smoking, and body mass index at minimum.
Both 95% CIs and P values are reported in situations in which upper or lower bound of CI involves 1.0.
Earlier UKB release of whole-exome sequencing on 45 186 participants.
Earlier UKB release of whole-exome sequencing on 37 657 participants, adjusted for age, age2, sex, smoking status, Townsend deprivation index, principal components of genetic ancestry, body mass index, hypertension, hyperlipidemia, and type 2 diabetes.