Figure 4.

Indels influencing gene expression and disease. (A) Distribution of relative frequencies (y-axis) with which variants drawn from several classes (see legend) explain a certain fraction of the variance in exonic gene expression levels (x-axis, measured by R², Pearson's correlation coefficient squared). For each variant, the exon showing the highest association was taken. Frequencies are shown relative to the distribution obtained from 100 permutations (for details, see Supplemental Information). (B) QQ plots of Spearman association P-values for coding indels by exon-level gene expression are stratified by indel length. Here, the enrichment of P-values for indels of length 1, 2, 4, and 5 relative to length 3 (green-line) is indicative of nonsense-mediated decay. For associations at an FDR of 0.20, this difference trended to significance for polarized indels (P = 0.10) and was significant for polarized and slippage indels (P = 0.04). (C) QQ plots of the distribution of linkage (r²) between GWA variants and nearby protein-coding variants (y-axis; four classes of variants), against a background distribution obtained from randomly drawn SNPs chosen to be controlled for excess linkage, and frequency-matched and chromosome-matched with the set of GWA SNPs (x-axis) (Supplemental Information). The central line and standard errors of these QQ curves were obtained by repeating the procedure 100 times. The SNP and indel r² distributions and standard errors (displayed as a cloud) tracked each other across all observed values.