title: Effect of genetic and environmental factors on protein biomarkers for common non-communicable disease and use of personally normalized plasma protein profiles (PNPPP).
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.
  
  
  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%.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Department of Immunology , Genetics, and Pathology, Biomedical Center, SciLifeLab Uppsala, Uppsala University , Uppsala , Sweden and.
authors.forename: Stefan
authors.initials: S
authors.lastname: Enroth
authors.affiliation: b Department of Medical Sciences , Uppsala University , Uppsala , Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Bosdotter Enroth
authors.affiliation: a Department of Immunology , Genetics, and Pathology, Biomedical Center, SciLifeLab Uppsala, Uppsala University , Uppsala , Sweden and.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Johansson
authors.affiliation: a Department of Immunology , Genetics, and Pathology, Biomedical Center, SciLifeLab Uppsala, Uppsala University , Uppsala , Sweden and.
authors.forename: Ulf
authors.initials: U
authors.lastname: Gyllensten
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood*; D001798:Blood Proteins / Q000032:analysis* / Q000235:genetics; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D004194:Disease / Q000145:classification / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods / Q000706:statistics & numerical data; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D020543:Proteome / Q000032:analysis / Q000235:genetics; D012907:Smoking
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D020543:Proteome
keywords: Non-communicable diseases; normalization; plasma protein biomarkers; proximity extension assay