Rare genetic variants confer the highest increased risk of type 2 diabetes to date

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Scientists at the University of Cambridge have identified rare genetic variants (carried by one in 3,000 people) that have a greater impact on the risk of developing type 2 diabetes than any previously identified genetic effect.

Type 2 it is believed to be driven in part by inheritance , but many of these genes are still unknown. Previous large-scale studies have relied on efficient “matrix genotyping” methods to measure genetic variations throughout the genome. This approach usually does a good job of capturing common genetic differences between people, although individually these only confer small increases. .

Recent technical advances have allowed for a more complete genetic measurement by reading the complete DNA sequences of more than 20,000 genes encoding proteins in humans. Proteins are essential molecules that allow our body to function. In particular, this new approach has made it possible to study the impact on a large scale for the first time on various diseases, including type 2 diabetes.

In studying data from more than 200,000 adults in the UK Biobank study, researchers in the Epidemiology Unit of the Cambridge University Medical Research Council (MRC) used this approach to identify genetic variants associated with the loss of Y chromosome. It is a known biomarker of biological aging that occurs in a small proportion of white blood cells circulating in men and indicates a weakening of the body’s cell repair systems. This biomarker has previously been linked to age-related diseases such as type 2 diabetes and cancer.

In the results published today in Communications on Nature, the researchers identified rare variants in the GIGYF1 gene that substantially increase the susceptibility to Y chromosome loss and also increase an individual’s risk of developing type 2 diabetes sixfold. In contrast, the usual variants associated with type 2 diabetes confer a much more modest increase in risk, usually much less than double.

Approximately 1 in 3,000 individuals carries this GIGYF1 genetic variant. The risk of developing type 2 diabetes is 30%, compared to 5% of the general population. In addition, people wearing these variants had other signs of more widespread aging, including weaker muscle strength and more body fat.

GIGYF1 is thought to control cell growth factor and insulin signaling. The researchers say their findings identify it as a potential target for future studies to understand the common links between metabolic and cellular aging and to report on future treatments.

Dr. John Perry, of the MRC Epidemiology Unit and lead author of the paper, said: “Reading an individual’s DNA is a powerful way to identify genetic variants that increase the risk of developing certain diseases. “In complex diseases such as type 2 diabetes, many variants play a role, but often only increase our risk by a small amount. This particular variant, while rare, has a large impact on an individual’s risk.”

Professor Nick Wareham, director of the MRC epidemiology unit, added: “Our findings highlight the exciting scientific potential of sequencing the genomes of a large number of people. We are confident that this approach will bring a new and rich in informative genetic discoveries help us better understand common diseases like type 2 diabetes. By doing so, we can offer better ways to treat or even prevent the disease. ”

Ongoing research will aim to understand how the loss of function variants in GIGYF1 leads to such a substantial increase in the risk of developing type 2 diabetes. Their future research will also examine other links between biomarkers of biological aging in adults. and metabolic disorders.


Genetic tools help identify a cellular culprit for type 1 diabetes


More information:
Zhao, Y. et al. Loss of GIGYF1 function is associated with clonal mosaicism and adverse metabolic health. Communications on Nature 2021; July 7, 2021; DOI: 10.1038 / s41467-021-24504-i

Citation: Rare genetic variants confer the highest increased risk of type 2 diabetes to date (2021, July 7) recovered on July 7, 2021 at https://medicalxpress.com/news/2021-07-rare-genetic- variants-confer-largest. html

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