TY - JOUR T1 - Genomic variation. Impact of regulatory variation from RNA to protein. JF - Science Y1 - 2015 A1 - Battle, Alexis A1 - Khan, Zia A1 - Wang, Sidney H A1 - Mitrano, Amy A1 - Ford, Michael J A1 - Pritchard, Jonathan K A1 - Gilad, Yoav KW - 3' Flanking Region KW - 5' Flanking Region KW - Cell Line KW - Exons KW - Gene Expression Regulation KW - Genetic Variation KW - HUMANS KW - PHENOTYPE KW - Protein Biosynthesis KW - Quantitative Trait Loci KW - Ribosomes KW - RNA, Messenger KW - Transcription, Genetic AB -

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.

VL - 347 CP - 6222 M3 - 10.1126/science.1260793 ER -