Stefan Enroth1, Sofia Bosdotter Enroth2, Åsa Johansson1, Ulf Gyllensten1. 1. a Department of Immunology , Genetics, and Pathology, Biomedical Center, SciLifeLab Uppsala, Uppsala University , Uppsala , Sweden and. 2. b Department of Medical Sciences , Uppsala University , Uppsala , Sweden.
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.
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
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