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Identification of g...
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Johansson, ÅsaUppsala universitet,Genomik,Uppsala kliniska forskningscentrum (UCR)
(author)
Identification of genetic variants influencing the human plasma proteome
- Article/chapterEnglish2013
Publisher, publication year, extent ...
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2013-03-04
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Proceedings of the National Academy of Sciences,2013
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-200115
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-200115URI
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https://doi.org/10.1073/pnas.1217238110DOI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Genetic variants influencing the transcriptome have been extensively studied. However, the impact of the genetic factors on the human proteome is largely unexplored, mainly due to lack of suitable high-throughput methods. Here we present unique and comprehensive identification of genetic variants affecting the human plasma protein profile by combining high-throughput and high-resolution mass spectrometry (MS) with genome-wide SNP data. We identified and quantified the abundance of 1,056 tryptic-digested peptides, representing 163 proteins in the plasma of 1,060 individuals from two population-based cohorts. The abundance level of almost one-fifth (19%) of the peptides was found to be heritable, with heritability ranging from 0.08 to 0.43. The levels of 60 peptides from 25 proteins, 15% of the proteins studied, were influenced by cis-acting SNPs. We identified and replicated individual cis-acting SNPs (combined P value ranging from 3.1 x 10(-52) to 2.9 x 10(-12)) influencing 11 peptides from 5 individual proteins. These SNPs represent both regulatory SNPs and nonsynonymous changes defining well-studied disease alleles such as the epsilon 4 allele of apolipoprotein E (APOE), which has been shown to increase risk of Alzheimer's disease. Our results show that high-throughput mass spectrometry represents a promising method for large-scale characterization of the human proteome, allowing for both quantification and sequencing of individual proteins. Abundance and peptide composition of a protein plays an important role in the etiology, diagnosis, and treatment of a number of diseases. A better understanding of the genetic impact on the plasma proteome is therefore important for evaluating potential biomarkers and therapeutic agents for common diseases.
Subject headings and genre
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protein quantitative trait loci
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population proteomics
Added entries (persons, corporate bodies, meetings, titles ...)
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Enroth, StefanUppsala universitet,Genomik(Swepub:uu)stenr451
(author)
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Palmblad, Magnus
(author)
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Deelder, Andre M.
(author)
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Bergquist, JonasUppsala universitet,Analytisk kemi(Swepub:uu)jbe25356
(author)
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Gyllensten, UlfUppsala universitet,Genomik(Swepub:uu)ulfgyll
(author)
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Uppsala universitetGenomik
(creator_code:org_t)
Related titles
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In:Proceedings of the National Academy of Sciences of the United States of America: Proceedings of the National Academy of Sciences110:12, s. 4673-46780027-84241091-6490
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