A genome-wide perspective of genetic variation in human metabolism View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-02

AUTHORS

Thomas Illig, Christian Gieger, Guangju Zhai, Werner Römisch-Margl, Rui Wang-Sattler, Cornelia Prehn, Elisabeth Altmaier, Gabi Kastenmüller, Bernet S Kato, Hans-Werner Mewes, Thomas Meitinger, Martin Hrabé de Angelis, Florian Kronenberg, Nicole Soranzo, H-Erich Wichmann, Tim D Spector, Jerzy Adamski, Karsten Suhre

ABSTRACT

Serum metabolite concentrations provide a direct readout of biological processes in the human body, and they are associated with disorders such as cardiovascular and metabolic diseases. We present a genome-wide association study (GWAS) of 163 metabolic traits measured in human blood from 1,809 participants from the KORA population, with replication in 422 participants of the TwinsUK cohort. For eight out of nine replicated loci (FADS1, ELOVL2, ACADS, ACADM, ACADL, SPTLC3, ETFDH and SLC16A9), the genetic variant is located in or near genes encoding enzymes or solute carriers whose functions match the associating metabolic traits. In our study, the use of metabolite concentration ratios as proxies for enzymatic reaction rates reduced the variance and yielded robust statistical associations with P values ranging from 3 x 10(-24) to 6.5 x 10(-179). These loci explained 5.6%-36.3% of the observed variance in metabolite concentrations. For several loci, associations with clinically relevant parameters have been reported previously. More... »

PAGES

137-141

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng.507

DOI

http://dx.doi.org/10.1038/ng.507

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1003091868

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/20037589


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