Version history

{
  "pmid": "27309819",
  "doi": "10.1038/nature18270",
  "abstract": "1. Nature. 2016 Jun 23;534(7608):500-5. doi: 10.1038/nature18270. Epub 2016 Jun\n15.\n\nDefining the consequences of genetic variation on a proteome-wide scale.\n\nChick JM(1), Munger SC(2), Simecek P(2), Huttlin EL(1), Choi K(2), Gatti DM(2), \nRaghupathy N(2), Svenson KL(2), Churchill GA(2), Gygi SP(1).\n\nAuthor information:\n(1)Harvard Medical School, Boston, Massachusetts 02115, USA.\n(2)The Jackson Laboratory, Bar Harbor, Maine 04609, USA.\n\nErratum in\n    Nature. 2022 Jun;606(7915):E16. doi: 10.1038/s41586-022-04920-w.\n\nGenetic variation modulates protein expression through both transcriptional and \npost-transcriptional mechanisms. To characterize the consequences of natural \ngenetic diversity on the proteome, here we combine a multiplexed, mass \nspectrometry-based method for protein quantification with an emerging outbred \nmouse model containing extensive genetic variation from eight inbred founder \nstrains. By measuring genome-wide transcript and protein expression in livers \nfrom 192 Diversity outbred mice, we identify 2,866 protein quantitative trait \nloci (pQTL) with twice as many local as distant genetic variants. These data \nsupport distinct transcriptional and post-transcriptional models underlying the \nobserved pQTL effects. Using a sensitive approach to mediation analysis, we \noften identified a second protein or transcript as the causal mediator of \ndistant pQTL. Our analysis reveals an extensive network of direct \nprotein-protein interactions. Finally, we show that local genotype can provide \naccurate predictions of protein abundance in an independent cohort of \ncollaborative cross mice.\n\nDOI: 10.1038/nature18270\nPMCID: PMC5292866\nPMID: 27309819 [Indexed for MEDLINE]",
  "journal": "Nature",
  "year": 2016,
  "authors": "Chick JM, Munger SC, Simecek P, Huttlin EL, Choi K, Gatti DM, Raghupathy N, Svenson KL, Churchill GA, Gygi SP",
  "url": "https://pubmed.ncbi.nlm.nih.gov/27309819",
  "external_ids": {
    "doi": "10.1038/nature18270",
    "pmid": "27309819"
  },
  "citation_count": 1,
  "domain": "neurodegeneration"
}