Fig. 5: Splicing-mediated NMD contributes to complex trait biology.
From: Global impact of unproductive splicing on human gene expression
a, QQ plot of multiple sclerosis GWAS signal, grouped by categories of SNPs. p-sQTLs that impact the balance of protein-coding isoforms and u-sQTLs that impact usage of unproductive splice junctions are similarly inflated for GWAS signals. b, Fraction of GWAS loci that colocalize with various sets of molQTLs in each of 45 blood or immune-related traits. Number of loci for which colocalization was attempted is indicated at the top of each column. ‘Other combinations’ includes loci that colocalize with alternative polyadenylation QTLs, hQTLs and sQTLs or other combinations that may include sQTLs and other molQTLs and are difficult to interpret mechanistically. c, Histogram of usage of unique sQTL junctions that colocalize with a GWAS signal, grouped by sQTL type. Intronic PSI (junction read count divided by most abundant junction in LeafCutter cluster) for each junction was summarized as the median from steady-state RNA samples which are homozygous for the PSI-increasing allele. Many GWAS sQTLs, especially u-sQTLs, have low PSI, even in samples with genotypes that favor higher usage. d, Effect size (β) of sQTLs and eQTLs for distinct u-sQTLs that colocalize with a GWAS signal. Correlation was summarized with Spearman’s rho coefficient and two-sided significance test.
