title: Genomic variation. Impact of regulatory variation from RNA to protein.
abstract: The phenotypic consequences of expression quantitative trait loci (eQTLs) are presumably due to their effects on protein expression levels. Yet the impact of genetic variation, including eQTLs, on protein levels remains poorly understood. To address this, we mapped genetic variants that are associated with eQTLs, ribosome occupancy (rQTLs), or protein abundance (pQTLs). We found that most QTLs are associated with transcript expression levels, with consequent effects on ribosome and protein levels. However, eQTLs tend to have significantly reduced effect sizes on protein levels, which suggests that their potential impact on downstream phenotypes is often attenuated or buffered. Additionally, we identified a class of cis QTLs that affect protein abundance with little or no effect on messenger RNA or ribosome levels, which suggests that they may arise from differences in posttranslational regulation.
authors: Department of Genetics, Stanford University, Stanford, CA 94305, USA. Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
authors: Alexis
authors: A
authors: Battle
authors: Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
authors: Zia
authors: Z
authors: Khan
authors: Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
authors: Sidney H
authors: SH
authors: Wang
authors: Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
authors: Amy
authors: A
authors: Mitrano
authors: MS Bioworks, LLC, 3950 Varsity Drive, Ann Arbor, MI 48108, USA.
authors: Michael J
authors: MJ
authors: Ford
authors: Department of Genetics, Stanford University, Stanford, CA 94305, USA. Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA. Department of Biology, Stanford University, Stanford, CA 94305, USA. pritch@stanford.edu gilad@uchicago.edu.
authors: Jonathan K
authors: JK
authors: Pritchard
authors: Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA. pritch@stanford.edu gilad@uchicago.edu.
authors: Yoav
authors: Y
authors: Gilad
mesh_terms: D024509:3' Flanking Region; D024506:5' Flanking Region; D002460:Cell Line; D005091:Exons; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006801:Humans; D010641:Phenotype; D014176:Protein Biosynthesis / Q000235:genetics*; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000235:genetics*; D012270:Ribosomes / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger
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