Cited by 364Genetic Associations and EpidemiologyAdvanced Proteomics Techniques and ApplicationsGenetic Mapping and Diversity in Plants and Animals

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Variation and genetic control of protein abundance in humans

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Wu, Linfeng, Candille, Sophie I., Choi, Yoonha, Xie, Dan, Jiang, Lihua, Li-Pook-Than, Jennifer, Tang, Hua, Snyder, Michael·2013·Nature

DOI 10.1038/nature12223PMC PMC3789121

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Abstract

Gene expression differs among individuals and populations and is thought to be a major determinant of phenotypic variation. Although variation and genetic loci responsible for RNA expression levels have been analysed extensively in human populations, our knowledge is limited regarding the differences in human protein abundance and the genetic basis for this difference. Variation in messenger RNA expression is not a perfect surrogate for protein expression because the latter is influenced by an array of post-transcriptional regulatory mechanisms, and, empirically, the correlation between protein and mRNA levels is generally modest. Here we used isobaric tag-based quantitative mass spectrometry to determine relative protein levels of 5,953 genes in lymphoblastoid cell lines from 95 diverse individuals genotyped in the HapMap Project. We found that protein levels are heritable molecular phenotypes that exhibit considerable variation between individuals, populations and sexes. Levels of specific sets of proteins involved in the same biological process covary among individuals, indicating that these processes are tightly regulated at the protein level. We identified cis-pQTLs (protein quantitative trait loci), including variants not detected by previous transcriptome studies. This study demonstrates the feasibility of high-throughput human proteome quantification that, when integrated with DNA variation and transcriptome information, adds a new dimension to the characterization of gene expression regulation.

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Authors: Wu, L., Candille, S. I., Choi, Y., Xie, D., Jiang, L., Li-Pook-Than, J., Tang, H., & Snyder, M.
Affiliations: Stanford Medicine (US)
Corresponding author: Tang, Hua
Snyder, Michael
ORCID: Choi, Yoonha
Xie, Dan
Jiang, Lihua
Tang, Hua
Snyder, Michael
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2013-05-15
Volume: 499
Issue: 7456
Pages: 79-82
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature12223
PMC: PMC3789121
OpenAlex: W2073109785
Cited by: 364
References: 25
Citations by year: 2026: 6 · 2025: 16 · 2024: 25 · 2023: 18 · 2022: 26 · 2021: 25 · 2020: 21 · 2019: 37 · 2018: 31 · 2017: 24 · 2016: 31 · 2015: 46 · 2014: 44 · 2013: 14
FWCI: 29.86
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: National Institutes of Health
National Heart, Lung, and Blood Institute (U01HL107393)
National Human Genome Research Institute (P50HG002357)
National Institute of General Medical Sciences (R01GM073059)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
Keywords: protein abundance, protein quantitative trait loci, cis-pQTL, interindividual variability, heritability, post-transcriptional regulation, mRNA-protein correlation, gene expression regulation, lymphoblastoid cell lines, sex differences, population variation, HapMap
MeSH terms: Cell Line, Ethnicity, Female, Gene Expression Regulation, Genotype, Humans, Male, Phenotype, RNA, Messenger, Mass Spectrometry, Protein Biosynthesis, Genetic Variation, Proteome, Gene Expression Profiling, Quantitative Trait Loci, Proteomics, Transcriptome, HapMap Project

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Variation and genetic control of protein abundance in humans

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