Quantitative variability of 342 plasma proteins in a human twin population

Yansheng Liu, Alfonso Buil, Ben C. Collins, Ludovic CJ Gillet, Lorenz C. Blum, Lin-Yang Cheng, Olga Vitek, Jeppe Mouritsen, Genevieve Lachance, Tim D. Spector, Emmanouil T. Dermitzakis, Ruedi Aebersold

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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. Synopsis The degree and origins of the abundance variability of 342 human plasma proteins are analyzed by a longitudinal twin design and SWATH mass spectrometry. The results suggest genetic control and longitudinal variation affect protein levels and biological processes to different degrees. We used the highly accurate and reproducible SWATH mass spectrometry technique to quantify 342 unique plasma proteins in 232 plasma samples collected longitudinally from pairs of monozygotic and dizygotic twins at intervals of 2–7 years.The observed total quantitative variability of human plasma proteome is dissected to its root causes, genes, environment and longitudinal factors.The roles of the heritable, environmental and longitudinal determinants in controlling plasma protein levels are different for different proteins and functional clusters, strongly suggesting that the plasma concentrations of clinical biomarkers need to be calibrated against genetic and temporal factors.We further identified 13 cis‐SNPs significantly influencing the level of specific plasma proteins as protein quantitative trait loci (pQTLs), and five of them are associated with gene expression QTLs (eQTLs) in human tissues.
Original languageEnglish
Article number786
Number of pages19
JournalMolecular systems biology
Volume11
Issue number2
DOIs
Publication statusPublished - 04 Feb 2015

Keywords

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

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