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Mol Syst Biol. 2015 Feb 4;11(1):786. doi: 10.15252/msb.20145728.

Quantitative variability of 342 plasma proteins in a human twin population.

Author information

1
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland liu@imsb.biol.ethz.ch aebersold@imsb.biol.ethz.ch.
2
Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland.
3
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
4
Department of Statistics and Department of Computer Science, Purdue University, West Lafayette, IN, USA.
5
Department of Twin Research and Genetic Epidemiology, King's College London St Tomas' Hospital Campus, London, UK.
6
Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland Faculty of Science, University of Zurich, Zurich, Switzerland liu@imsb.biol.ethz.ch aebersold@imsb.biol.ethz.ch.

Abstract

The degree and the origins of quantitative variability of most human plasma proteins are largely unknown. Because the twin study design provides a natural opportunity to estimate the relative contribution of heritability and environment to different traits in human population, we applied here the highly accurate and reproducible SWATH mass spectrometry technique to quantify 1,904 peptides defining 342 unique plasma proteins in 232 plasma samples collected longitudinally from pairs of monozygotic and dizygotic twins at intervals of 2-7 years, and proportioned the observed total quantitative variability to its root causes, genes, and environmental and longitudinal factors. The data indicate that different proteins show vastly different patterns of abundance variability among humans and that genetic control and longitudinal variation affect protein levels and biological processes to different degrees. The data further strongly suggest that the plasma concentrations of clinical biomarkers need to be calibrated against genetic and temporal factors. Moreover, we identified 13 cis-SNPs significantly influencing the level of specific plasma proteins. These results therefore have immediate implications for the effective design of blood-based biomarker studies.

KEYWORDS:

SWATH‐MS; heritability; longitudinal variability; plasma biomarkers; twin study

PMID:
25652787
PMCID:
PMC4358658
DOI:
10.15252/msb.20145728
[Indexed for MEDLINE]
Free PMC Article

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