Krumsiek J, Mittelstrass K, Do KT, Stueckler F, Ried J, Adamski J, Peters A, Illig T, Kronenberg F, Friedrich N, Nauck M, Pietzner M, Mook-Kanamori DO, Suhre K, Gieger C, Grallert H, Theis FJ, Kastenmueller G (2015)
Publication Type: Journal article
Publication year: 2015
Book Volume: 11
Pages Range: 1815-1833
Journal Issue: 6
DOI: 10.1007/s11306-015-0829-0
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.
APA:
Krumsiek, J., Mittelstrass, K., Do, K.T., Stueckler, F., Ried, J., Adamski, J.,... Kastenmueller, G. (2015). Gender-specific pathway differences in the human serum metabolome. Metabolomics, 11(6), 1815-1833. https://doi.org/10.1007/s11306-015-0829-0
MLA:
Krumsiek, Jan, et al. "Gender-specific pathway differences in the human serum metabolome." Metabolomics 11.6 (2015): 1815-1833.
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