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Ried, J.S. ; Shin, S.Y.* ; Krumsiek, J. ; Illig, T. ; Theis, F.J. ; Spector, T.D.* ; Adamski, J. ; Wichmann, H.-E. ; Strauch, K. ; Soranzo, N.* ; Suhre, K. ; Gieger, C.

Novel genetic associations with serum level metabolites identified by phenotype set enrichment analyses.

Hum. Mol. Genet. 23, 5847-5857 (2014)
Verlagsversion Postprint Post-Print DOI PMC
Open Access Green
Availability of standardized metabolite panels and genome-wide single nucleotide polymorphism (SNP) data endorse the comprehensive analysis of gene-metabolite association. Currently, many studies use genome-wide association analysis to investigate the genetic effects on single metabolites (mGWAS) separately. Such studies have identified several loci that are associated not only with one but with multiple metabolites, facilitated by the fact that metabolite panels often include metabolites of the same or related pathways. Strategies that analyse several phenotypes in a combined way were shown to be able to detect additional genetic loci. One of those methods is the phenotype set enrichment analysis (PSEA) that tests sets of metabolites for enrichment at genes. Here we applied PSEA on two different panels of serum metabolites together with genome-wide data. All analyses were performed as a two-step identification-validation approach, using data from the population-based KORA cohort and the TwinsUK study. In addition to confirming genes that were already known from mGWAS, we were able to identify and validate twelve new genes. Knowledge about gene function was supported by the enriched metabolite sets. For loci with unknown gene functions, the results suggest a function that is interrelated with the metabolites, and hint at the underlying pathways.
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GAC Icb_metabo Icb_MIMOmics
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Genome-wide Association; Cell-growth; Loci; Traits
Sprache englisch
Veröffentlichungsjahr 2014
HGF-Berichtsjahr 2014
ISSN (print) / ISBN 0964-6906
e-ISSN 1460-2083
Zeitschrift Human Molecular Genetics
Quellenangaben Band: 23, Heft: 21, Seiten: 5847-5857 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Verlagsort Oxford
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology (EPI)
Molekulare Endokrinologie und Metabolismus (MEM)
Institute of Computational Biology (ICB)
Institute of Bioinformatics and Systems Biology (IBIS)
German Center for Diabetes Reseach (DZD)
POF Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30202 - Environmental Health
30201 - Metabolic Health
30205 - Bioengineering and Digital Health
30505 - New Technologies for Biomedical Discoveries
Forschungsfeld(er) Genetics and Epidemiology
Enabling and Novel Technologies
PSP-Element(e) G-504100-001
G-504091-001
G-505600-003
G-505600-001
G-503800-001
G-503700-001
G-504000-007
G-504090-001
PubMed ID 24927737
DOI 10.1093/hmg/ddu301
WOS ID WOS:000343203600022
Scopus ID 84911413446
Erfassungsdatum 2014-06-16
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