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. Author manuscript; available in PMC: 2023 Nov 1.
Published in final edited form as: NEJM Evid. 2023 Apr 25;2(5):10.1056/evidoa2200310. doi: 10.1056/evidoa2200310

Table 1.

Characteristics of UK Biobank Derivation Cohort

No CHIP/CCUS
(N = 182406)		 All CHIP/CCUS
(N = 11337)		 CHIP
(N = 10479)		 CCUS1
(N = 858)
Demographics, Duration of Follow-up, Prior Cancer History and Smoking Status
Sex
Female 100200 (54.9%) 6235 (55.0%) 5818 (55.5%) 417 (48.6%)
Male 82206 (45.1%) 5102 (45.0%) 4661 (44.5%) 441 (51.4%)
Age (years)
Median [IQR] 57.0 [50, 63] 62.0 [57, 66] 62.0 [57, 66] 62.0 [56, 66]
Follow-up time2 (years)
Median [IQR] 11.7 [10.8, 12.5] 11.6 [10.8, 12.4] 11.6 [10.8, 12.4] 11.2 [10.6, 12.1]
Any Smoking History
Yes 102085 (56.0%) 5703 (50.3%) 5272 (50.3%) 431 (50.2%)
No 80322 (44.0%) 5634 (49.7%) 5207 (49.7%) 427 (49.8%)
Prior Cancer History3
Prior Malignancy 9844 (5.4%) 908 (8.0%) 818 (7.8%) 90 (10.5%)
No Prior Malignancy 172562 (94.6%) 10429 (92.0%) 9804 (92.2%) 768 (89.5%)
Laboratory Values and Cytopenias 4
White Blood Cell Count (x109 cells/L)
Median [IQR] 6.68 [5.69, 7.85] 6.84 [5.77, 8.10] 6.90 [5.82, 8.10] 6.28 [4.87, 7.64]
Hemoglobin (g/dL)
Median [IQR] 14.1 [13.3, 15.0] 14.1 [13.4, 15.0] 14.2 [13.5, 15.1] 12.6 [11.7, 14.0]
Platelets (x109 cells/L)
Median [IQR] 247 [213, 286] 249 [213, 289] 250 [216, 290] 216 [142, 284]
Neutrophil Count (x109 cells/L)
Median [IQR] 4.03 [3.30, 4.95] 4.16 [3.36, 5.13] 4.20 [3.40, 5.15] 3.67 [2.59, 4.83]
Number of Cytopenias
0 169801 (93.1%) 10479 (92.4%) 10479 (100%) 0 (0%)
1 12106 (6.6%) 797 (7.0%) 0 (0%) 797 (92.9%)
2 464 (0.3%) 57 (0.5%) 0 (0%) 57 (6.6%)
3 35 (0.0%) 4 (0.04%) 0 (0%) 4 (0.5%)
Anemia
No 174878 (95.9%) 10837 (95.6%) 10479 (100%) 358 (41.7%)
Yes 7528 (4.1%) 500 (4.4%) 0 (0%) 500 (58.3%)
Thrombocytopenia
No 178330 (97.8%) 11040 (97.4%) 10479 (100%) 561 (65.4%)
Yes 4076 (2.2%) 297 (2.6%) 0 (0%) 297 (34.6%)
Neutropenia
No 180871 (99.2%) 11211 (98.9%) 10479 (100%) 732 (85.3%)
Yes 1535 (0.8%) 126 (1.1%) 0 (0%) 126 (14.7%)
Mean Corpuscular Volume (fL)
Median [IQR] 91.3 [88.6, 93.9] 91.4 [88.8, 94.1] 91.4 [88.9, 94.1] 90.6 [86.7, 94.1]
Mean Platelet Volume (fL)
Median [IQR] 9.20 [8.58, 9.94] 9.18 [8.51, 9.92] 9.15 [8.50, 9.90] 9.47 [8.70, 10.60]
Red Cell Distribution Width (%)
Median [IQR] 13.3 [12.9, 13.9] 13.4 [13.0, 14.0] 13.4 [12.9, 13.9] 14.0 [13.3, 15.1]

A derivation cohort of 193,744 UK Biobank participants were evaluated by whole exome sequencing for presence or absence of clonal hematopoiesis (CH) and further classified as having clonal hematopoiesis of indeterminate potential (CHIP) or clonal cytopenia of undetermined significance (CCUS) based on the absence or presence of cytopenia.

1

Cytopenias were defined such that individuals classified as CCUS had one or more of the following: anemia (hemoglobin <13 g/dL for male participants and hemoglobin <12 g/dL for female participants), thrombocytopenia (platelet count of <150K/uL) or neutropenia (absolute neutrophil count <1.8 K/uL).

2

Follow-up time is the number of years from sequencing to death or last follow-up (January 2021), whichever is earliest.

3

Prior Cancer History is defined as history of solid or lymphoid malignancy in the years prior to enrollment in study based on aggregated self-report and hospital records by International Classification of Disease (ICD-10) code (codes listed in Supplemental Table 1). Individuals with prior histories of myeloid malignancy were excluded. Cancer types contributing to prior cancer history in this population are indicated in Supplemental Table 3.

4

Hematologic parameters obtained from complete blood count and differential obtained at the time of sequencing.

Categorical variables are summarized by the number of events, N, and proportion (%). Continuous variables are summarized using median and interquartile range (IQR).