Gender-specific pathway differences in the human serum metabolome. Academic Article uri icon

Overview

abstract

  • The susceptibility for various diseases as well as the response to treatments differ considerably between men and women. As a basis for a gender-specific personalized healthcare, an extensive characterization of the molecular differences between the two genders is required. In the present study, we conducted a large-scale metabolomics analysis of 507 metabolic markers measured in serum of 1756 participants from the German KORA F4 study (903 females and 853 males). One-third of the metabolites show significant differences between males and females. A pathway analysis revealed strong differences in steroid metabolism, fatty acids and further lipids, a large fraction of amino acids, oxidative phosphorylation, purine metabolism and gamma-glutamyl dipeptides. We then extended this analysis by a network-based clustering approach. Metabolite interactions were estimated using Gaussian graphical models to get an unbiased, fully data-driven metabolic network representation. This approach is not limited to possibly arbitrary pathway boundaries and can even include poorly or uncharacterized metabolites. The network analysis revealed several strongly gender-regulated submodules across different pathways. Finally, a gender-stratified genome-wide association study was performed to determine whether the observed gender differences are caused by dimorphisms in the effects of genetic polymorphisms on the metabolome. With only a single genome-wide significant hit, our results suggest that this scenario is not the case. In summary, we report an extensive characterization and interpretation of gender-specific differences of the human serum metabolome, providing a broad basis for future analyses.

authors

  • Krumsiek, Jan
  • Mittelstrass, Kirstin
  • Do, Kieu Trinh
  • Stückler, Ferdinand
  • Ried, Janina
  • Adamski, Jerzy
  • Peters, Annette
  • Illig, Thomas
  • Kronenberg, Florian
  • Friedrich, Nele
  • Nauck, Matthias
  • Pietzner, Maik
  • Mook-Kanamori, Dennis O
  • Suhre, Karsten
  • Gieger, Christian
  • Grallert, Harald
  • Theis, Fabian J
  • Kastenmüller, Gabi

publication date

  • August 4, 2015

Identity

PubMed Central ID

  • PMC4605991

Scopus Document Identifier

  • 0028179077

Digital Object Identifier (DOI)

  • 10.1161/01.ATV.14.4.567

PubMed ID

  • 26491425

Additional Document Info

volume

  • 11

issue

  • 6