title: Omics for prediction of environmental health effects: Blood leukocyte-based cross-omic profiling reliably predicts diseases associated with tobacco smoking.
abstract: The utility of blood-based omic profiles for linking environmental exposures to their potential health effects was evaluated in 649 individuals, drawn from the general population, in relation to tobacco smoking, an exposure with well-characterised health effects. Using disease connectivity analysis, we found that the combination of smoking-modified, genome-wide gene (including miRNA) expression and DNA methylation profiles predicts with remarkable reliability most diseases and conditions independently known to be causally associated with smoking (indicative estimates of sensitivity and positive predictive value 94% and 84%, respectively). Bioinformatics analysis reveals the importance of a small number of smoking-modified, master-regulatory genes and suggest a central role for altered ubiquitination. The smoking-induced gene expression profiles overlap significantly with profiles present in blood cells of patients with lung cancer or coronary heart disease, diseases strongly associated with tobacco smoking. These results provide proof-of-principle support to the suggestion that omic profiling in peripheral blood has the potential of identifying early, disease-related perturbations caused by toxic exposures and may be a useful tool in hazard and risk assessment.
authors.affiliation: National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, 48 Vas. Constantinou Ave., Athens 11635, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Georgiadis
authors.affiliation: Maastricht University, Minderbroedersberg 4-6, 6211 LK, Maastricht, Netherlands.
authors.forename: Dennie G
authors.initials: DG
authors.lastname: Hebels
authors.affiliation: National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, 48 Vas. Constantinou Ave., Athens 11635, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Valavanis
authors.affiliation: National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, 48 Vas. Constantinou Ave., Athens 11635, Greece.
authors.forename: Irene
authors.initials: I
authors.lastname: Liampa
authors.affiliation: Department of Biobank Research, and Occupational and Environmental Medicine, Department of Public Health and Clinical Medicine, Umeå University, Sweden.
authors.forename: Ingvar A
authors.initials: IA
authors.lastname: Bergdahl
authors.affiliation: Nutrition Research, Department of Public Health and Clinical Medicine, Umeå University, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Johansson
authors.affiliation: The Institute for Cancer Research and Prevention, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.affiliation: MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, W2 1PG, UK.
authors.forename: Marc
authors.initials: M
authors.lastname: Chadeau-Hyam
authors.affiliation: National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, 48 Vas. Constantinou Ave., Athens 11635, Greece.
authors.forename: Aristotelis
authors.initials: A
authors.lastname: Chatziioannou
authors.affiliation: Maastricht University, Minderbroedersberg 4-6, 6211 LK, Maastricht, Netherlands.
authors.forename: Danyel G J
authors.initials: DG
authors.lastname: Jennen
authors.affiliation: Maastricht University, Minderbroedersberg 4-6, 6211 LK, Maastricht, Netherlands.
authors.forename: Julian
authors.initials: J
authors.lastname: Krauskopf
authors.affiliation: Maastricht University, Minderbroedersberg 4-6, 6211 LK, Maastricht, Netherlands.
authors.forename: Marlon J
authors.initials: MJ
authors.lastname: Jetten
authors.affiliation: Maastricht University, Minderbroedersberg 4-6, 6211 LK, Maastricht, Netherlands.
authors.forename: Jos C S
authors.initials: JC
authors.lastname: Kleinjans
authors.affiliation: MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, W2 1PG, UK.
authors.forename: Paolo
authors.initials: P
authors.lastname: Vineis
authors.affiliation: National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, 48 Vas. Constantinou Ave., Athens 11635, Greece.
authors.forename: Soterios A
authors.initials: SA
authors.lastname: Kyrtopoulos
mesh_terms: D019295:Computational Biology / Q000379:methods; D003324:Coronary Artery Disease / Q000235:genetics; D019175:DNA Methylation; D004781:Environmental Exposure; D004782:Environmental Health; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012907:Smoking / Q000097:blood / Q000235:genetics*
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