Publication Date:
2016-04-30
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Yang I -- van de Geijn, Bryce -- Raj, Anil -- Knowles, David A -- Petti, Allegra A -- Golan, David -- Gilad, Yoav -- Pritchard, Jonathan K -- R01MH084703/MH/NIMH NIH HHS/ -- R01MH101825/MH/NIMH NIH HHS/ -- U01HG007036/HG/NHGRI NIH HHS/ -- U54CA149145/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Apr 29;352(6285):600-4. doi: 10.1126/science.aad9417. Epub 2016 Apr 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Stanford University, Stanford, CA, USA. ; Department of Human Genetics, University of Chicago, Chicago, IL, USA. ; Department of Computer Science, Stanford University, Stanford, CA, USA. Department of Radiology, Stanford University, Stanford, CA, USA. ; Genome Institute, Washington University in St. Louis, St. Louis, MO, USA. ; Department of Human Genetics, University of Chicago, Chicago, IL, USA. gilad@uchicago.edu pritch@stanford.edu. ; Department of Genetics, Stanford University, Stanford, CA, USA. Department of Biology, Stanford University, Stanford, CA, USA. Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. gilad@uchicago.edu pritch@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27126046" target="_blank"〉PubMed〈/a〉
Keywords:
Cell Line
;
Chromatin/metabolism
;
*Gene Expression Regulation
;
*Genetic Variation
;
Genome-Wide Association Study
;
Humans
;
Immune System Diseases/*genetics
;
Lymphocytes/immunology
;
Phenotype
;
Polymorphism, Single Nucleotide
;
*Quantitative Trait Loci
;
RNA Splicing/*genetics
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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