RNA splicing is a primary link between genetic variation and disease

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