RNA splicing is a primary link between genetic variation and disease

被引：409

作者：

Li, Yang I. ^{[1
]}

van de Geijn, Bryce ^{[2
]}

Raj, Anil ^{[1
]}

Knowles, David A. ^{[3
,4
]}

Petti, Allegra A. ^{[5
]}

Golan, David ^{[1
]}

Gilad, Yoav ^{[2
]}

Pritchard, Jonathan K. ^{[1
,6
,7
]}

机构：

[1] Stanford Univ, Dept Genet, Stanford, CA 94305 USA

[2] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA

[3] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA

[4] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA

[5] Washington Univ, Genome Inst, St Louis, MO USA

[6] Stanford Univ, Dept Biol, Stanford, CA 94305 USA

[7] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA

来源：

SCIENCE | 2016年 / 352卷 / 6285期

关键词：

GENOME-WIDE ASSOCIATION; EXPRESSION VARIATION; HUMANS; MECHANISMS;

D O I：

10.1126/science.aad9417

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 similar to 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.

引用

页码：600 / 604

页数：5

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