Effect of Genetic and Environmental Factors on Protein Biomarkers for Common Non-Communicable Disease and Use of Personally Normalized Plasma Protein Profiles (PNPPP)

Biomarkers. 2015;20(6-7):355-64. doi: 10.3109/1354750X.2015.1093546. Epub 2015 Nov 9.

Abstract

Objective: To study the impact of genetic and lifestyle factors on protein biomarkers and develop personally normalized plasma protein profiles (PNPPP) controlling for non-disease-related variance.

Materials and methods: Proximity extension assays were used to measure 145 proteins in 632 controls and 344 cases with non-communicable diseases.

Results: Genetic and lifestyle factors explained 20-88% of the variation in healthy controls. Adjusting for these factors reduced the number of candidate biomarkers by 63%.

Conclusion: PNPPP efficiently controls for non-disease-related variance, allowing both for efficient discovery of novel biomarkers and for covariate-independent linear cut-offs suitable for clinical use.

Keywords: Non-communicable diseases; normalization; plasma protein biomarkers; proximity extension assay.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Analysis of Variance
  • Biomarkers / blood*
  • Blood Proteins / analysis*
  • Blood Proteins / genetics
  • Body Mass Index
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / genetics
  • Disease / classification
  • Disease / genetics
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genome-Wide Association Study / methods
  • Genome-Wide Association Study / statistics & numerical data
  • Genotype
  • Humans
  • Inflammation / blood
  • Inflammation / diagnosis
  • Inflammation / genetics
  • Male
  • Middle Aged
  • Neoplasms / blood*
  • Neoplasms / diagnosis
  • Neoplasms / genetics
  • Polymorphism, Single Nucleotide
  • Proteome / analysis
  • Proteome / genetics
  • Smoking

Substances

  • Biomarkers
  • Blood Proteins
  • Proteome