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Identification of g...
Identification of genetic variants influencing the human plasma proteome
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- Johansson, Åsa (author)
- Uppsala universitet,Genomik,Uppsala kliniska forskningscentrum (UCR)
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- Enroth, Stefan (author)
- Uppsala universitet,Genomik
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Palmblad, Magnus (author)
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Deelder, Andre M. (author)
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- Bergquist, Jonas (author)
- Uppsala universitet,Analytisk kemi
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- Gyllensten, Ulf (author)
- Uppsala universitet,Genomik
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(creator_code:org_t)
- 2013-03-04
- 2013
- English.
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:12, s. 4673-4678
- Related links:
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https://www.pnas.org...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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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.
Keyword
- protein quantitative trait loci
- population proteomics
Publication and Content Type
- ref (subject category)
- art (subject category)
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