Inhaltsverzeichnis - Mathematisches Institut der Universität zu Köln

DMV Tagung 2011 - Köln, 19. - 22. September
Christian Gieger
Institute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
The role of genetically determined metabotypes in the genetics of complex traits and
polygenic disorders
Metabolite concentrations provide a direct readout of biological processes in the human body, and are
associated with disorders such as cardiovascular and metabolic diseases. We have identified common
genetic polymorphisms that alter an individual’s metabolic capacities. Knowledge of these genetically determined
metabotypes in the human population is key to identify the contributions and interactions of
genetic and environmental factors in the etiology of complex diseases. I will present a genome-wide association
study with 163 metabolic traits, covering a biologically relevant panel of amino acids, sugars,
acylcarnitines, and phospholipids, using 1809 participants from the KORA population. Most often, the genetic
variant is located in or near enzyme or solute carrier coding genes, where the associating metabolic
traits match the proteins’ function. The analysis of such a dataset is a major computational effort. We
calculated more than 26,000 separate genome-wide association studies, in which we associated 500,000
single nucleotide polymorphisms with 163 metabolite concentrations as well as all possible 26,406 metabolite
concentration ratios. Statistical modelling is not trivial as metabolite concentrations are highly
correlated due to common and connected metabolic pathways. In summary, this study allowed us to draw
a systemic perspective of the genetic variation that is found in metabolism.
Literatur
Gieger C, Geistlinger L, Altmaier E, Hrabe de Angelis M, Kronenberg F, Meitinger T, Mewes HW, Wichmann
HE, Weinberger KM, Adamski J, Illig T, Suhre K (2008). Genetics meets metabolomics: a genomewide
association study of metabolite profiles in human serum. PLoS Genetics 4(11):e1000282
Illig T, Gieger C, Zhai G, Römisch-Margl W, Wang-Sattler R, Prehn C, Altmaier E, Kastenmüller G, Kato
BS, Mewes HW, Meitinger T, Hrabe de Angelis M, Kronenberg F, Soranzo N, Wichmann HE, Spector TD,
Adamski J, Suhre K (2010). A genome-wide perspective of genetic variation in human metabolism. Nature
Genetics 42(2), 137-41.
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