Detection of genes differentially expressed between VHLR200W homozygotes and VHL wildtype control individuals.
A. The quantile-quantile plot for d-statistic of differential expression between 21 WT individuals and 24 VHLR200W homozygotes without controlling for serum ferritin variation. Blue lines represent d-statistic cutoffs for calling genes at FDR 0.05 and orange lines at FDR 0.01. Solid black line represents diagonal. Green points represent significant calls at FDR 0.01. The majority of genes exhibit a modest up-shift relative to the diagonal line at FDR 0.05, implying up-regulation.
B. For genes called at FDR 0.01 in A, expression level was fitted by a linear model including VHL genotype and log (ferritin) as two explanatory variables; for 1336 genes, genotype effect was no longer significant at nominal P =0.05. This indicates that ferritin variation confounded genotype effect.
C. The quantile-quantile plot for d-statistic of differential expression between 17 WT individuals and 8 VHLR200W homozygotes matched for serum ferritin concentration. Orange lines represent d-statistic cutoffs for calling genes at FDR 0.05. Green points represent significant calls at FDR 0.05.