RNA splicing is a primary link between genetic variation and disease

Yang I. Li, Bryce Van De Geijn, Anil Raj, David A. Knowles, Allegra A. Petti, David Golan, Yoav Gilad, Jonathan K. Pritchard

Research output: Contribution to journalArticlepeer-review

376 Scopus citations


Noncoding variants play a central role in the genetics of complex traits, but we still lack a full understanding of the molecular pathways through which they act.We quantified the contribution of cis-acting genetic effects at all major stages of gene regulation from chromatin to proteins, in Yoruba lymphoblastoid cell lines (LCLs). About 65% of expression quantitative trait loci (eQTLs) have primary effects on chromatin, whereas the remaining eQTLs are enriched in transcribed regions. Using a novel method, we also detected 2893 splicing QTLs, most of which have little or no effect on gene-level expression. These splicing QTLs are major contributors to complex traits, roughly on a par with variants that affect gene expression levels. Our study provides a comprehensive view of the mechanisms linking genetic variation to variation in human gene regulation.

Original languageEnglish
Pages (from-to)600-604
Number of pages5
Issue number6285
StatePublished - Apr 29 2016


Dive into the research topics of 'RNA splicing is a primary link between genetic variation and disease'. Together they form a unique fingerprint.

Cite this