Effect of genetic and environmental factors on protein biomarkers for common non-communicable disease and use of personally normalized plasma protein profiles (PNPPP)

<i>Objective</i>: To study the impact of genetic and lifestyle factors on protein biomarkers and develop <i>personally normalized plasma protein profiles</i> (PNPPP) controlling for non-disease-related variance. <i>Materials and methods</i>: Proximity extension assays were used to measure 145 proteins in 632 controls and 344 cases with non-communicable diseases. <i>Results</i>: 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%. <i>Conclusion</i>: 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.