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  3. Medizin - Open Access LMU - Teil 15/22 Podcast
  4. Genetics Meets Metabolomics
The rapidly evolving field of metabolomics aims at a comprehensive
measurement of ideally all endogenous metabolites in a cell or body
fluid. It thereby provides a functional readout of the
physiological state of the human body. Genetic variants that
associate with changes in the homeostasis of key lipids,
carbohydrates, or amino acids are not only expected to display much
larger effect sizes due to their direct involvement in metabolite
conversion modification, but should also provide access to the
biochemical context of such variations, in particular when enzyme
coding genes are concerned. To test this hypothesis, we conducted
what is, to the best of our knowledge, the first GWA study with
metabolomics based on the quantitative measurement of 363
metabolites in serum of 284 male participants of the KORA study. We
found associations of frequent single nucleotide polymorphisms
(SNPs) with considerable differences in the metabolic homeostasis
of the human body, explaining up to 12% of the observed variance.
Using ratios of certain metabolite concentrations as a proxy for
enzymatic activity, up to 28% of the variance can be explained
(p-values 10(-16) to 10(-21)). We identified four genetic variants
in genes coding for enzymes (FADS1, LIPC, SCAD, MCAD) where the
corresponding metabolic phenotype (metabotype) clearly matches the
biochemical pathways in which these enzymes are active. Our results
suggest that common genetic polymorphisms induce major
differentiations in the metabolic make-up of the human population.
This may lead to a novel approach to personalized health care based
on a combination of genotyping and metabolic characterization.
These genetically determined metabotypes may subscribe the risk for
a certain medical phenotype, the response to a given drug
treatment, or the reaction to a nutritional intervention or
environmental challenge.

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„Genetics Meets Metabolomics“

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