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Inborn variation in metabolism

Nature Genetics volume 42, pages 97–98 (2010)Cite this article

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Advances in analytical biochemistry have recently made it possible to obtain global snapshots of metabolism. A new study couples such technology with genome-wide genetic analysis to explore inherited variation in human metabolism.

Inborn errors of metabolism refer to single-gene disorders wherein loss of the function of a single enzyme results in altered levels of linked reaction metabolites, generally substrates or products of biochemical reactions. The term was coined by Archibald Garrod, who first elucidated the biochemical basis of disorders such as alkaptonuria over 100 years ago. Since then, hundreds of inborn errors of metabolism have been characterized. Garrod predicted that inborn errors were “merely extreme examples of variations of chemical behavior which are probably everywhere present in minor degrees1” and that this “chemical individuality [confers] predisposition to and immunities from the various mishaps which are spoken of as diseases”2. Indeed, the levels of many metabolites do show substantial interindividual variation, some of which is likely to be influenced by genetic variation. On page 137 of this issue, Karsten Suhre and colleagues report an early implementation of a strategy to systematically explore the genetic basis of chemical individuality3.

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Figure 1: Mendelian randomization experiment to test whether genetic alteration of a metabolic pathway plays a causal role in disease.

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Authors and Affiliations

  1. Vamsi K. Mootha is at the Harvard Medical School Department of Systems Biology, Massachusetts General Hospital, Boston, and the Broad Institute Metabolism Initiative, Cambridge, Massachusetts, USA.,

    Vamsi K Mootha

  2. Joel N. Hirschhorn is at the Harvard Medical School Department of Genetics, Children's Hospital, Boston, and the Broad Institute Metabolism Initiative, Cambridge, Massachusetts, USA.,

    Joel N Hirschhorn

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  1. Vamsi K Mootha
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  2. Joel N Hirschhorn
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Correspondence to Vamsi K Mootha or Joel N Hirschhorn.

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Mootha, V., Hirschhorn, J. Inborn variation in metabolism. Nat Genet 42, 97–98 (2010). https://doi.org/10.1038/ng0210-97

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