A genome-wide perspective of genetic variation in human metabolism
Open accessAbstract
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.
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Genome-wide analysis studies have identified loci associated with variations in endogenous metabolite concentrations, and many of these genes coded for metabolic enzymes.
“A number of loci associated with variations in the concentration of endogenous metabolites could be identified in genome-wide analysis studies, and many of these genes were coding for metabolic enzymes (180-182).”
From The food metabolome: a window over dietary exposure (2014) · cites this paper as [181]
Genome-wide association studies of metabolite abundance identified relatively common alleles that accounted for significant fractions of variation in metabolite levels, sometimes more than 20% of total variance.
“Surprisingly, these studies identified a number of relatively common alleles that accounted for significant fractions of the variation in metabolite levels, sometimes more than 20% of the total variance (Gieger et al., 2008; Illig et al., 2010).”
From Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us? (2012) · cites this paper as Illig et al., 2010
Some polymorphisms associated with metabolite levels changed the coding sequence of a metabolic enzyme directly related to the variable metabolite.
“There were several examples in which a polymorphism changed the coding sequence of a metabolic enzyme directly related to the variable metabolite.”
From Cellular Metabolism and Disease: What Do Metabolic Outliers Teach Us? (2012) · cites this paper as Illig et al., 2010
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- Authors
- Illig, T., Gieger, C., Zhai, G., Römisch-Margl, W., Wang-Sattler, R., Prehn, C., Altmaier, E., Kastenmüller, G., Kato, B. S., Mewes, H.-W., Meitinger, T., de Angelis, M. H., Kronenberg, F., Soranzo, N., Wichmann, H.-E., Spector, T. D., Adamski, J., & Suhre, K.
- Affiliations
- Helmholtz Munich (DE)
- King's College London (GB)
- TUM Klinikum (DE)
- Innsbruck Medical University (AT)
- Corresponding author
- Suhre, Karsten
- ORCID
- Venue
- Nature Genetics
- Published
- 2009-12-27
- Volume
- 42
- Issue
- 2
- Pages
- 137-141
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC3773904
- OpenAlex
- W2006141598
- Cited by
- 653
- References
- 29
- Citations by year
- 2026: 10 · 2025: 23 · 2024: 26 · 2023: 16 · 2022: 33 · 2021: 27 · 2020: 41 · 2019: 32 · 2018: 48 · 2017: 35 · 2016: 42 · 2015: 63 · 2014: 55 · 2013: 59 · 2012: 70
- FWCI
- 27.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (King's College London) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion, other-oa)
- Site cant be reached (submittedVersion)
- Funders
- Wellcome Trust (091746)
- Biotechnology and Biological Sciences Research Council (G20234)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- serum metabolites, metabolic phenotypes, genetic variation, genome-wide association study, FADS1, ELOVL2, ACADS, ACADM, ACADL, ETFDH, solute carrier transporters, cardiovascular disease, metabolic disorders, kora, TwinsUK
- MeSH terms
- Delta-5 Fatty Acid Desaturase, United Kingdom, Humans, Genetic Variation, Reproducibility of Results, Genome, Human, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Metabolome, Genetic Loci
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