RNA splicing is a primary link between genetic variation and disease

TLDR

RNA splicing is a primary link between genetic variation and disease, as many disease-associated variants lack obvious effects on protein‑coding sequences. The study systematically analyzed how DNA variants influence gene regulation from chromatin state to protein function. They found that one‑third of expression quantitative trait loci act through transcriptional mechanisms rather than chromatin, that splice QTLs confer disease risk comparable to expression QTLs, and that posttranscriptional processes play a major role in translating genotype to phenotype. Li et al., Science, p.

Abstract

RNA splicing links genetics to disease Many genetic variants associated with disease have no apparent effect on any specific protein coding sequence. Li et al. systematically analyzed the effects of DNA variants on the main steps of gene regulation, from the chromatin state through protein function. One-third of expression quantitative train loci (QTLs) are mediated through transcriptional processes, not chromatin. Splice QTLs and expression QTLs are about comparable in their complex disease risk. Posttranscriptional mechanisms therefore play a large role in translating genotype to phenotype. Science , this issue p. 600