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Genetic map reveals influence of DNA on metabolism

New study reveals the role of metabolites in health and disease.

2025-10-03
(Press-News.org)

A new study, published today in Nature Genetics, created the largest genetic map of human metabolism, revealing new insights on the role of metabolites in health and disease and creating a blueprint for further research.

Humans vary from person to person, and so does our metabolism. Yet, it is difficult to quantify precisely how much your genetic code contributes to this variability.

Using data from half a million individuals through the UK Biobank, the authors examined the consequences of variation in our genetic code on blood levels of 250 small molecules including lipid levels, which are important for a healthy heart, or amino acids. The study is the result of a collaborative effort led by researchers at the Berlin Institute of Health @ Charité (BIH) and Queen Mary University of London.

By combining large-scale genetic data from European, African and Asian individuals living in the UK with detailed metabolomic measurements, the team systematically identified genes contributing to human metabolism. Results showed that genetic control of metabolites was very similar across ancestries and between men and women, which suggests that results and conclusions drawn from the study likely apply to most people. This included genes with previously unknown roles in metabolism, offering new insights in metabolic pathways and human health.

The study also provided insights into genes associated with metabolism that predispose to disease. They showed that the genetic control of blood metabolites overlaps with disease, demonstrating the relevance of such studies for human health and the importance of these metabolites in health and disease. For example, the authors newly identified a gene called VEGFA that possibly controls aspects of the denser form of cholesterol (HDL) which may help develop new medicines to prevent heart diseases. 

Studies of this magnitude are made possible by the emergence of biobanks worldwide. UK Biobank recruited half a million people with diverse backgrounds living in the UK and collected everyone’s genetic information as well as general information such as lifestyle and health variables. The authors took advantage of this large dataset to perform in-depth analyses, including as many individuals in the study as possible.

While genetics play a substantial part, the authors emphasize that metabolism is a mixed bag including modifiable factors such as lifestyle, diet and exercise whose influence cannot be underestimated for a healthy life.

Lead author Martijn Zoodsma, postdoctoral researcher at the BIH in Berlin, said: “We are now able to map systematically the genetic control of hundreds of blood molecules, at unprecedented scale. This provides a powerful reference to understand disease risk and identify genes that contribute to variability in metabolism.”

Senior author Maik Pietzner, Professor for Health Data Modelling at BIH and Queen Mary’s Precision Health University Research Institute (PHURI) added: “The development of blood lipid-lowering medications, such as statins, has saved numerous lives, but heart diseases remain the major killer. Our results highlight potential avenues that will hopefully lead to new medicines to prevent even more deaths from lipid plaques building in people's arteries.”

Senior author Claudia Langenberg, director of the Queen Mary’s PHURI, and head of the Computational Medicine group at the BIH, said: “Our study is a powerful demonstration of what can be achieved through academic-industry science partnerships. Nightingale Health’s technology has measured blood lipids and metabolites in the full UK Biobank cohort of 500,000 samples. This is the scale and commitment needed to robustly identify rare genetic variation underlying differences in human metabolism and health. Martijn’s work using these data has also revealed strong similarities between different ancestries or sexes of how our genes shape our metabolic individuality – a reminder that we are all human, and have much in common.”

 

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[Press-News.org] Genetic map reveals influence of DNA on metabolism
New study reveals the role of metabolites in health and disease.