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Plate IV.536 · Publications

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

Article in Human Molecular Genetics, 13 June 2014.

Open accessMetabolite, Association, Metabolomics Data

  1. Janina S. Ried
  2. So-Youn Shin
  3. Jan Krumsiek
  4. Thomas Illig
  5. Fabian J. Theis
  6. Tim D. Spector
  7. Jerzy Adamski
  8. H.-Erich Wichmann
  9. Konstantin Strauch
  10. Nicole Soranzo
  11. Karsten Suhre
  12. Christian Gieger

Abstract

Availability of standardized metabolite panels and genome-wide single-nucleotide polymorphism 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 12 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.

Cite

@article{ried2014novel,
  title = {{Novel genetic associations with serum level metabolites identified by phenotype set enrichment analyses}},
  author = {Ried, Janina S. and Shin, So-Youn and Krumsiek, Jan and Illig, Thomas and Theis, Fabian J. and Spector, Tim D. and Adamski, Jerzy and Wichmann, H.-Erich and Strauch, Konstantin and Soranzo, Nicole and Suhre, Karsten and Gieger, Christian},
  journal = {Human Molecular Genetics},
  publisher = {Oxford University Press (OUP)},
  year = {2014},
  month = jun,
  doi = {10.1093/hmg/ddu301},
  url = {https://doi.org/10.1093/hmg/ddu301},
  pmid = {24927737},
  pmcid = {PMC4271073}
}
.bib file