title: Metabonomic, transcriptomic, and genomic variation of a population cohort.
abstract: Comprehensive characterization of human tissues promises novel insights into the biological architecture of human diseases and traits. We assessed metabonomic, transcriptomic, and genomic variation for a large population-based cohort from the capital region of Finland. Network analyses identified a set of highly correlated genes, the lipid-leukocyte (LL) module, as having a prominent role in over 80 serum metabolites (of 134 measures quantified), including lipoprotein subclasses, lipids, and amino acids. Concurrent association with immune response markers suggested the LL module as a possible link between inflammation, metabolism, and adiposity. Further, genomic variation was used to generate a directed network and infer LL module's largely reactive nature to metabolites. Finally, gene co-expression in circulating leukocytes was shown to be dependent on serum metabolite concentrations, providing evidence for the hypothesis that the coherence of molecular networks themselves is conditional on environmental factors. These findings show the importance and opportunity of systematic molecular investigation of human population samples. To facilitate and encourage this investigation, the metabonomic, transcriptomic, and genomic data used in this study have been made available as a resource for the research community.
authors.affiliation: Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia. inouye@wehi.edu.au
authors.forename: Michael
authors.initials: M
authors.lastname: Inouye
authors.forename: Johannes
authors.initials: J
authors.lastname: Kettunen
authors.forename: Pasi
authors.initials: P
authors.lastname: Soininen
authors.forename: Kaisa
authors.initials: K
authors.lastname: Silander
authors.forename: Samuli
authors.initials: S
authors.lastname: Ripatti
authors.forename: Linda S
authors.initials: LS
authors.lastname: Kumpula
authors.forename: Eija
authors.initials: E
authors.lastname: Hämäläinen
authors.forename: Pekka
authors.initials: P
authors.lastname: Jousilahti
authors.forename: Antti J
authors.initials: AJ
authors.lastname: Kangas
authors.forename: Satu
authors.initials: S
authors.lastname: Männistö
authors.forename: Markku J
authors.initials: MJ
authors.lastname: Savolainen
authors.forename: Antti
authors.initials: A
authors.lastname: Jula
authors.forename: Jaana
authors.initials: J
authors.lastname: Leiviskä
authors.forename: Aarno
authors.initials: A
authors.lastname: Palotie
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
authors.forename: Mika
authors.initials: M
authors.lastname: Ala-Korpela
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
mesh_terms: D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000097:blood; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism; D030541:Databases, Genetic; D005260:Female; D005387:Finland; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000235:genetics; D014644:Genetic Variation; D015894:Genome, Human; D005838:Genotype; D000949:Histocompatibility Antigens Class II; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007962:Leukocytes / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D055432:Metabolomics; D008875:Middle Aged; D044382:Population Groups; D014280:Triglycerides / Q000097:blood
chemical_list: D001055:Apolipoproteins B; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D018836:Inflammation Mediators; D008075:Lipoproteins, HDL; D014280:Triglycerides; D002784:Cholesterol