Genetic Analysis of Human Traits In Vitro: Drug Response and Gene Expression in Lymphoblastoid Cell Lines (original) (raw)
Figure 4
RNA expression is correlated to SNPs and cellular traits.
198 unrelated individuals were whole-genome RNA profiled on the Affymetrix platform at the Broad Institute (“Broad RNA”) and independently on the Illumina platform at WTSI (“WTSI RNA”). The 1000 “best-measured” genes identified in Figure 3 were tested for correlation to SNPs and cellular traits. (A) For each tested gene, Broad RNA expression levels were rank-correlated to copy numbers of EBV, as determined by quantitative PCR. The correlation was expressed as rho2 and curves representing distributions of the rho2values are plotted. The green curve is the observed distribution of EBV-RNA correlations. The red curves represent 20 permuted distributions. The blue curve is the average of permuted distributions. The black curve is the difference between observed and permuted values and thus a lower bound (see Methods) of the fraction of genes correlated to EBV at a given rho2. Plot shows that ∼15% of expressed genes have >5% of their (rank) variance in expression explained by EBV levels. (B) For each tested gene, Broad RNA expression levels were correlated to baseline ATP levels determined by measuring Celltiter glo in mock-treated wells in the drug response assays. Curves representing the distribution of rho2 values were plotted for the tested genes as in (A). Plot shows that >25% of expressed genes have >5% of their variance in expression explained by ATP levels. (C) For each tested gene, Broad RNA expression levels were correlated to all SNPs with MAF>10% within a 0.15 Mb window around the gene, using the HapMap phase II data. Curves representing the distribution of the largest r2 value was plotted for each tested genes as in (A). Plot shows that >9% of genes have >5% of their variance in expression explained by SNPs in the Broad RNA dataset. (D) For each tested gene, Sanger RNA expression levels were correlated to all SNPs with MAF>10% within a 0.15 Mb window around the gene, using the HapMap phase II data. Curves representing the distribution of the strongest r2 value was plotted for each tested genes as in (C). Plot shows that >20% of genes have >5% of their variance in expression explained by SNPs in the WTSI RNA dataset. (E) For each tested gene, Broad RNA expression levels were correlated to EBV, growth rate, and relative ATP, and the strongest observed correlation among the 3 phenotypes was plotted. Strikingly, plot shows that >40% of genes have >5% of their variance in expression explained by one of these covariates. (F) For each tested gene, WTSI RNA expression levels were correlated to EBV, growth rate, and relative ATP, and the strongest observed correlation among the 3 phenotypes was plotted. Strikingly, plot shows that the effect of covariates in (E) is observable even when looking at a completely separate expression experiment, performed independently of covariate collection.