Nat Med: Identifies specific genes that control the body's metabolic personality and risk of developing disease

The concept of "chemical individuality" proposed by British scientist Archibald Edward Garrod helps to understand the molecular origin of human disease, and non-targeted high-throughput metabolomics techniques can also provide large-scale deep snapshot
information of human metabolism 。 Recently, a research report entitled "Rare and common genetic determinants of metabolic individuality and their effects on human health" published in the international journal Nature Medicine, scientists from Queen Mary College of London and other institutions found that More than 300 regions in the genome may help promote a person's "chemical fingerprint.
"

Each person has a "chemical fingerprint", the main feature of which is the composition of small molecules in the blood, such as fats or sugars, which are determined by the body's genes and external factors, often promoting which diseases the individual is prone to, and the severity of
the disease the individual suffers.
In this study, the researchers identified rare and common changes in the genetic code that affect the body's metabolic personality, as well as their impact
on the body's health and disease.
Researcher Adam Butterworth explains that through this study, we have elucidated the genetic control patterns of body metabolism based on hundreds of circulating small molecules, and revealed how these changes affect the occurrence
of a variety of diseases.

article, The researchers studied more than 14,000 participants from two major UK population studies (INTERVAL and EPIC-Norfolk) and measured levels of more than 900 small molecules in participants' blood samples whose genetic codes had been previously analyzed; the researchers then identified 330 genomic regions or associated with levels of 646 different metabolites, most of which were associated with several metabolites and vice versa
。 Crucially, the study will also help scientists reveal which metabolic changes contribute to individual diseases, and the researchers say that these metabolic "hotspots" in the genome may help them better understand which genes are associated with changes in molecular weight in the blood, and with these findings, researchers can reveal which protein changes contribute to the development of
human diseases such as breast cancer.

Identify specific genes
that control the body's metabolic personality and risk of developing disease.

Image source: Nature Medicine (2022).
DOI: 10.
1038/s41591-022-02046-0

Changes in metabolic hotspots in the genome not only play an important role in the body's healthy metabolism, but also in disease susceptibility, and researchers have also identified variants that can affect the action of drugs and the extent of their harmful effects; For example, the researchers found that about one-fifth of the studies found that participants carried mutations in the genetic code close to the DPYD gene, which encodes a special enzyme responsible for breaking down specific common cancer chemotherapy drugs, and that individuals carrying these genetic mutations have an increased risk of accumulating elevated levels of these drugs, which can have more serious effects
.

Researcher Claudia Langenberg said that mutations near genes that can be targeted by drugs may also provide us with clues about possible unwanted side effects, for example, we can reveal that drugs that reduce the conversion of steroid hormones in the body to combat male hair loss and prostatic hyperplasia may increase the risk of depression, and this is consistent
with the results reported from drug studies.

The researchers are excited that information about individual chemical fingerprints and the genomic variants that underpin them may help clinicians treat individual patients more effectively, and that researchers will need to conduct more in-depth studies to better map the genetic diversity of different populations to understand how genetic mutations differ between specific populations and the clinical effects
they produce.
(Biovalley Bioon.
com)

Original source:

Praveen Surendran,Isobel D Stewart,Victoria P W Au Yeung, et al.
 Rare and common genetic determinants of metabolic individuality and their effects on human health, Nature Medicine (2022).
DOI: 10.
1038/s41591-022-02046-0