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Suhre, K. ; Shin, S.Y.* ; Petersen, A.-K. ; Mohney, R.P.* ; Meredith, D.* ; Wägele, B. ; Altmaier, E. ; CARDIoGRAM Consortium (Lichtner, P. ; Eckstein, G.N. ; Fischer, G. ; Strom, T.M. ; Peters, A. ; Holle, R. ; John, J.) ; Deloukas, P.* ; Erdmann, J.* ; Grundberg, E.* ; Hammond, C.J.* ; Hrabě de Angelis, M. ; Kastenmüller, G. ; Köttgen, A.* ; Kronenberg, F.* ; Mangino, M.* ; Meisinger, C. ; Meitinger, T. ; Mewes, H.-W. ; Milburn, M.V.* ; Prehn, C. ; Raffler, J. ; Ried, J.S. ; Römisch-Margl, W. ; Samani, N.J.* ; Small, K.S.* ; Wichmann, H.-E. ; Zhai, G.* ; Illig, T. ; Spector, T.D.* ; Adamski, J. ; Soranzo, N.* ; Gieger, C.

Human metabolic individuality in biomedical and pharmaceutical research.

Nature 477, 54-60 (2011)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Genome-wide association studies (GWAS) have identified many risk loci for complex diseases, but effect sizes are typically small and information on the underlying biological processes is often lacking. Associations with metabolic traits as functional intermediates can overcome these problems and potentially inform individualized therapy. Here we report a comprehensive analysis of genotype-dependent metabolic phenotypes using a GWAS with non-targeted metabolomics. We identified 37 genetic loci associated with blood metabolite concentrations, of which 25 show effect sizes that are unusually high for GWAS and account for 10-60% differences in metabolite levels per allele copy. Our associations provide new functional insights for many disease-related associations that have been reported in previous studies, including those for cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, venous thromboembolism and Crohn's disease. The study advances our knowledge of the genetic basis of metabolic individuality in humans and generates many new hypotheses for biomedical and pharmaceutical research.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Genome-wide Association; Chronic kidney-disease; Genetic-variation; Transporter family; Bilirubin levels; Loci; Variants; Risk; Metaanalysis; Contribute
ISSN (print) / ISBN 0028-0836
e-ISSN 1476-4687
Zeitschrift Nature
Quellenangaben Band: 477, Heft: 7362, Seiten: 54-60 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Bioinformatics and Systems Biology (IBIS)
Institute of Genetic Epidemiology (IGE)
Institute of Experimental Genetics (IEG)
Molekulare Endokrinologie und Metabolismus (MEM)
Institute of Human Genetics (IHG)
Research Unit Molecular Epidemiology (AME)
CF Comparative Medicine (CF-Comparative Medicine)