Extended Data Fig. 9: GWAS/sQTL colocalizations that also colocalize with eQTL have characteristics consistent with AS-NMD.

(a) sQTLs/GWAS colocalizations are more likely to come from u-sQTLs than p-sQTLs if the host gene eQTL also colocalizes in multi-trait colocalization analysis. P value from hypergeometric test for over-representation. (b) PSI distribution of introns as cumulative distribution plot for sQTLs that colocalize with eQTL and GWAS (sQTL+eQTL colocs) versus those that only colocalize with GWAS (sQTL colocs). We estimate PSI by averaging across samples with shared genotypes, either high/high genotypes or low/low genotypes (thus, avoiding confounding PSI estimates with different allele frequencies between datasets). sQTLs in unproductive introns that are sQTL+eQTLs have smaller PSI in steady-state RNA than naRNA, consistent with splicing-mediated decay at these GWAS loci transcripts. P-value for two-sided Mann-Whitney test. (c) Effect sizes of sQTLs that colocalize with GWAS, grouped by whether the GWAS signal also colocalizes with an eQTL (sQTL+eQTL colocs), whether it solely colocalizes with sQTL, or whether it also colocalizes with some other combination of traits (that is, sQTL + hQTL) in multi-trait colocalization analysis. Each junction is plotted once, even if it colocalizes with multiple GWAS loci across multiple traits. Correlation of effect sizes summarized as spearman rho correlation coefficient and two-sided correlation test P-value.