PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Gieger, C. ; Geistlinger, L. ; Altmaier, E. ; Hrabě de Angelis, M. ; Kronenberg, F.* ; Meitinger, T. ; Mewes, H.-W. ; Wichmann, H.-E. ; Weinberger, K.M.* ; Adamski, J. ; Illig, T. ; Suhre, K.

Genetics meets metabolomics: A genome-wide association study of metabolite profiles in human serum.

PLoS Genet. 4:e1000282 (2008)
Verlagsversion Volltext DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The rapidly evolving field of metabolomics aims at a comprehensive measurement of ideally all endogenous metabolites in a cell or body fluid. It thereby provides a functional readout of the physiological state of the human body. Genetic variants that associate with changes in the homeostasis of key lipids, carbohydrates, or amino acids are not only expected to display much larger effect sizes due to their direct involvement in metabolite conversion modification, but should also provide access to the biochemical context of such variations, in particular when enzyme coding genes are concerned. To test this hypothesis, we conducted what is, to the best of our knowledge, the first GWA study with metabolomics based on the quantitative measurement of 363 metabolites in serum of 284 male participants of the KORA study. We found associations of frequent single nucleotide polymorphisms (SNPs) with considerable differences in the metabolic homeostasis of the human body, explaining up to 12% of the observed variance. Using ratios of certain metabolite concentrations as a proxy for enzymatic activity, up to 28% of the variance can be explained (p-values 10(-16) to 10(-21)). We identified four genetic variants in genes coding for enzymes (FADS1, LIPC, SCAD, MCAD) where the corresponding metabolic phenotype (metabotype) clearly matches the biochemical pathways in which these enzymes are active. Our results suggest that common genetic polymorphisms induce major differentiations in the metabolic make-up of the human population. This may lead to a novel approach to personalized health care based on a combination of genotyping and metabolic characterization. These genetically determined metabotypes may subscribe the risk for a certain medical phenotype, the response to a given drug treatment, or the reaction to a nutritional intervention or environmental challenge.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
8.721
0.880
433
546
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Genetics; metabolomics; study; metabolite profiles; human serum; CORONARY-ARTERY-DISEASE; CARDIOVASCULAR-DISEASE; PHENOTYPES; POPULATION; LOCI; METABONOMICS; LIPIDOMICS; GENOTYPES; VARIANTS; SPECTRUM
Sprache englisch
Veröffentlichungsjahr 2008
HGF-Berichtsjahr 0
ISSN (print) / ISBN 1553-7390
e-ISSN 1553-7404
Zeitschrift PLoS Genetics
Quellenangaben Band: 4, Heft: 11, Seiten: , Artikelnummer: e1000282 Supplement: ,
Verlag Public Library of Science (PLoS)
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology (EPI)
Institute of Experimental Genetics (IEG)
Institute of Bioinformatics and Systems Biology (IBIS)
Institute of Human Genetics (IHG)
POF Topic(s) 30503 - Chronic Diseases of the Lung and Allergies
30201 - Metabolic Health
30505 - New Technologies for Biomedical Discoveries
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30202 - Environmental Health
Forschungsfeld(er) Genetics and Epidemiology
Enabling and Novel Technologies
PSP-Element(e) G-503900-003
G-500600-004
G-503700-001
G-500700-001
G-504090-001
PubMed ID 19043545
DOI 10.1371/journal.pgen.1000282
WOS ID 000261481000036
Scopus ID 57149114936
Erfassungsdatum 2008-12-19
[➜Korrektur melden]