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Gene carried by one in 3000 men increases risk of type 2 diabetes

12 July 2021
Appeared in BioNews 1103

Rare genetic variants in the GIGYF1 gene that increase an man's risk of developing type 2 diabetes by six-fold, have been identified by researchers at the University of Cambridge.

The GIGYF1 gene is already known to be associated with cell growth factor signalling and the regulation of insulin, which could partly explain the role of variants in the development of type 2 diabetes. Researchers have now discovered that variants of GIGYF1 increase susceptibility to loss of the Y chromosome in adult men and is linked to signs of ageing such as more body fat and weaker muscle strength, in a study published in Nature Communications.

'Reading an individual's DNA is a powerful way of identifying genetic variants that increase our risk of developing certain diseases. For complex diseases such as type 2 diabetes, many variants play a role, but often only increasing our risk by a tiny amount. This particular variant, while rare, has a big impact on an individual's risk,' said Dr John Perry, programme leader and Medical Research Council investigator at the University of Cambridge, who is an author of this research. 

Researchers analysed data from over 200,000 adult men in the UK Biobank study in order to identify genetic variants associated with the loss of the Y chromosome. The loss of the Y chromosome from circulating white blood cells is a known biomarker of biological ageing that has been previously linked with age-related diseases such as cancer and type 2 diabetes.

The researchers conducted an exome-sequence genome-wide association study in order to identify rare genetic variants. They discovered that approximately one in 3000 people carry a GIGYF1 genetic variant and the risk of these individuals developing type 2 diabetes is around 30 percent compared to the wider population which have around a five percent risk of developing this condition. 

This effect is larger than that of other genetic variants known to increase risk of developing type 2 diabetes, which are thought to double risk. 

Further research will be conducted to investigate the mechanisms via which variants in GIGYF1 lead to an increased risk of developing type 2 diabetes.

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