Table 2. Annotation of clusters with disease outcomes.
| Cluster 1 (n = 657) | Cluster 2 (n = 437) | Cluster 3 (n = 364) | Cluster 4 (n = 341) | Cluster 5 (n = 273) | Cluster 6 (n = 91) | Cluster 7 (n = 52) | Cluster 8 (n = 47) | |
|---|---|---|---|---|---|---|---|---|
| Hemoglobin Genotype (%) | ||||||||
| HbSS | 396 (60.6) | 68 (15.6) | 279 (76.6) | 270 (79.2) | 22 (8.1) | 56 (61.5) | 37 (71.2) | 45 (95.7) |
| HbSC | 42 (6.4) | 205 (46.9) | 3 (0.8) | 5 (1.5) | 194 (71.1) | 13 (14.3) | 4 (7.7) | 0 (0.0) |
| HbSS-α thalassemia | 167 (25.5) | 50 (11.4) | 62 (17.0) | 62 (18.2) | 18 (6.6) | 17 (18.7) | 11 (21.2) | 1 (2.1) |
| HbS-β+ thalassemia | 49 (7.5) | 114 (26.1) | 20 (5.5) | 4 (1.2) | 39 (14.3) | 5 (5.5) | 0 (0.0) | 1 (2.1) |
| Mortality1 HR (p) | Reference | 0.57 (0.17) | 1.24 (0.37) | 0.51 (0.03) | 1.73 (0.18) | 1.42 (0.39) | 1.08 (0.86) | 0.88 (0.81) |
| Stroke2 HR (p) | Reference | 0.26 (0.082) | 1.62 (0.15) | 0.66 (0.35) | 0.91 (0.88) | 0.74 (0.68) | 1.37 (0.67) | 0.60 (0.62) |
| Seizure1 HR (p) | Reference | 1.30 (0.46) | 1.04 (0.91) | 0.45 (0.06) | 0.58 (0.35) | 2.27 (0.042) | 2.21 (0.11) | 2.36 (0.082) |
| Leg Ulcer1 HR (p) | Reference | 0.57 (0.18) | 1.50 (0.067) | 1.00 (0.98) | 0.51 (0.30) | 1.55 (0.29) | 1.14 (0.75) | 1.35 (0.50) |
| Acute Chest Syndrom1 HR (p) | Reference | 0.75 (0.04)8 | 1.06 (0.61) | 0.90 (0.38) | 0.96 (0.83) | 1.53 (0.01) | 1.06 (0.81) | 1.06 (0.81) |
| Avascular Necrosis1 HR (p) | Reference | 1.08 (0.68) | 0.84 (0.34) | 0.67 (0.033) | 1.31 (0.24) | 2.12 (0.0029) | 0.58 (0.17) | 0.49 (0.17) |
| Time Until First Painful Episode1 HR (p) | Reference | 0.77 (0.026) | 0.87 (0.18) | 0.94 (0.51) | 1.13 (0.39) | 1.00 (0.99) | 0.50 (0.0095) | 0.78 (0.30) |
| Having a Painful Episode OR3,4 (p) | Reference | 0.68 (0.00046) | 0.97 (0.76) | 0.97 (0.74) | 0.87 (0.27) | 0.96 (0.78) | 1.09 (0.69) | 1.04 (0.87) |
| Having a Severe Painful Episode OR5 (p) | Reference | 0.82 (0.27) | 0.76 (0.074) | 0.60 (0.00048) | 0.96 (0.86) | 1.05 (0.83) | 1.74 (0.20) | 1.23 (0.56) |
| Fetal Hemoglobin Trajectory 6 (p) | 9.5% | 1.54 (0.00) | 0.83 (0.004) | 1.20 (0.006) | 0.98 (0.80) | 0.82 (0.05) | 0.91 (0.58) | 0.48 (0.00) |
| Hemolytic anemia7 (p) | Reference | -0.37 (0.00) | 0.18 (0.03) | 0.17 (0.07) | -0.25 (0.01) | 0.22 (0.07) | 0.25 (0.16) | 0.53 (0.07) |
Hazard ratios and p-values obtained from Cox Proportional Regression controlling for baseline age, sex, and hemoglobin genotype
HR adjusted for baseline age, sex and whether patients are HbSS or not
Odds ratios and p-values obtained from logistic regression controlling for baseline age, sex, and hemoglobin genotype
Model adjusted for HbSS or other genotype.
Odds ratios and p-values obtained from longitudinal data using GEE and logistic regression controlling for baseline age, sex, and hemoglobin genotype
Regression coefficients estimated from longitudinal data using GEE and an additive cluster effect. The value in Cluster 1 is the average HbF at age 8, and the values in the other clusters are fold changes compared to Cluster 1.
Regression coefficients estimated from longitudinal data using GEE and an additive cluster effect. Cluster effects are changes in hemolytic score compared to Cluster 1.Positive score = more hemolysis.
The levels of significance were not corrected for multiple testing and a p-value < 0.006 would be required for maintaining statistical significance after Bonferroni correction.