Quantitative variability of 342 plasma proteins in a human twin population

Molecular Systems Biology

Yansheng Liu¹  Alfonso Buil²  Ben C Collins¹  Ludovic CJ Gillet¹  Lorenz C Blum¹  Lin-Yang Cheng³  Olga Vitek³  Jeppe Mouritsen¹  Genevieve Lachance⁴  Tim D Spector⁴  Emmanouil T Dermitzakis² 

[1] Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland;Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland;Department of Statistics and Department of Computer Science, Purdue University, West Lafayette, IN, USA;Department of Twin Research and Genetic Epidemiology, King's College London, St Tomas' Hospital Campus, London, UK

关键词: heritability;    longitudinal variability;    plasma biomarkers;    SWATH‐MS;    twin study;   

DOI  :  10.15252/msb.20145728

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 The Authors. Published under the terms of the CC BY 4.0 license

Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.