A genomewide perspective of genetic variation in human metabolism

By Thomas Illig, C. Gieger, G. Zhai, W. Römisch-Margl, R. Wang-Sattler, C. Prehn, E. Altmaier, G. Kastenmüller, B. Kato, Hans-Werner Mewes and 8 more. Nature Genetics, 2009

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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 × 10−24 to 6.5 × 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.

Subfields: Genetics, Molecular Biology, Rheumatology

View Paper: https://www.semanticscholar.org/paper/d9b91b643e81eb24f8efed5b5e85b23c20d1b5b2

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Citations in the corpus

Tobacco Smoking Leads to Extensive Genome-Wide Changes in DNA Methylation (2013, methodology): “The standardized examinations applied in the survey (4261 participants) have been described in detail elsewhere [46–48].”
Gaussian graphical modeling reconstructs pathway reactions from high-throughput metabolomics data (2011, methodology): “This indicates that a high heterogeneity of metabolic states in a population data set like the KORA cohort might be beneficial rather than problematic for our approach.”
New IBD genetics: common pathways with other diseases (2011, background): “32 141 FADS1 provides a link between Crohn’s disease,(32) fasting serum glucose levels,(142) hypercholesterolaemia (HDL and LDL cholesterol and triglycerides),(136) 143 and serum metabolites.(144) While the gut flora has not been directly studied in the context of T2DM, we may look to studies in obe”
MultiPhen: Joint Model of Multiple Phenotypes Can Increase Discovery in GWAS (2012, methodology): “[6] investigated genetic association with metabolites and all metabolite ratios, using metabolite ratios as proxies for enzymatic reaction rates.”