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RNA splicing is a primary link between genetic variation and disease.

ABSTRACT: 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.

SUBMITTER: Li YI

PROVIDER: S-EPMC5182069 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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RNA splicing is a primary link between genetic variation and disease.

Li Yang I YI van de Geijn Bryce B Raj Anil A Knowles David A DA Petti Allegra A AA Golan David D Gilad Yoav Y Pritchard Jonathan K JK

Science (New York, N.Y.) 20160428 6285

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 ...[more]

PMID: 27126046

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