Fig. 4: RNA-Binding protein associations with sQTLs.
a Volcano plot depicting the effect size (x-axis) and -log10 p-values (y-axis) of RBP sites enrichment in sQTLs identified in PBS- or FN-f-treated chondrocytes. P-values and odds ratios were calculated using QTLtools Fenrich module with 1000 permutations (“Methods”). The enrichment analysis uses a two-sided empirical permutation test to determine whether RBP binding sites are over- or under-represented in regions containing sQTLs compared to control regions, without adjustment for multiple comparisons. Data points are shown for p-value < 0.05 and odds ratios > 1. b Analysis of AATF RBP binding and expression correlation with the rs11871958 sQTL in the SNHG29 gene. Locus zoom plots show -log10(p-value) of SNP-splicing associations across the genomic region in PBS and FN-f conditions (PBS: p = 1.48 × 10−21, β = −0.9; FN-f: p = 1.06 × 10−24, β = −0.99, minor allele frequency = 0.1832). These association statistics were calculated using QTLtools. The middle track displays AATF eCLIP signal (RPM) with the sQTL SNP location highlighted. Box plots show normalized PSI values by rs11871958 genotype (n = 202 samples from 101 biologically independent donors, each providing PBS and FN-f samples). Box plots display median (center line), 25th–75th percentiles (box), minimum-maximum values within 1.5× interquartile range (whiskers), and outliers (points). The scatter plot shows correlation between AATF gene expression (VST-normalized DESeq values) and normalized PSI values across all samples (R2 = 0.408, p = 2.22 × 10−28). Pearson correlation was used with a two-sided linear regression model to calculate the p-value, without adjustment for multiple comparisons. c Analysis of EFTUD2 RBP binding and expression correlation with the rs6809764 sQTL in the PCYT1A gene, following the same format as panel b. QTLtools statistics for this sQTL: PBS (p = 4.65 × 10−8, β = 0.44); FN-f (p = 2.29 × 10−7, β = 0.522, minor allele frequency = 0.3911). The correlation between EFTUD2 gene expression and normalized PSI values (n = 202 samples) shows R2 = 0.164, p = 7.84 × 10−9, calculated using the same statistical methods.
