Figure 1.

Sickle cell disease impacts gene expression genome-wide. (A) The first two expression principal components (ePC) from PC analysis of the discovery and replication phase samples, and in the combined dataset. Individuals are coloured according to Hb genotype (HbSS, blue; HbSC, green; and Controls, red), SCD severity score (SV, red to blue indicates high to low severity) and clinical status effect (ClinStatus, yellow; E, purple, Ctls, red). (B) One-way hierarchical clustering of the genome-wide gene expression correlation matrix for the combined dataset (n = 311). The heat map shows the clustering of individual expression profiles based on similarity. The highest level of clustering is observed for the Hb genotype effect followed by SCD severity score. (C) Variance component analysis (VCA) of the first three expression PCs (ePC1-3) explaining 36, 37, and 37% of the total variance in the discovery, replication, and in the combined dataset. The two main variables that explain this variance are Hb genotype and clinical status effect. The proportion of the variance explained by each variable is similar in the discovery, replication and combined datasets. VCA of SCD patients alone shows that the proportion of the variance explained by clinical status was similar to that when the controls were included but the proportion of the variance explained by Hb genotype dropped by 25–50%. See also Figure S4.