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Rare Genetic Variant Leads to Six-Fold Increase in Diabetes Risk

NEW evidence has emerged linking the presence of a rare genetic variant to an increased risk of developing Type 2 diabetes mellitus. The variant, estimated to be carried by one in 3,000 people, has been identified to have a larger impact on susceptibility of the disease than any other known genetic variant.

The onset of Type 2 diabetes mellitus is understood to be partially caused by the inheritance of genetic factors, many of which are still unknown to scientists. New approaches have advanced from previously used methods and now rely on reading the complete DNA sequences of the 20,000 protein-coding genes found in humans. This technique allows scientists to study the impact of rare genetic variants on diseases on a larger scale than ever.

Researchers from the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge, UK, studied data from the UK Biobank study to detect genetic variants associated with the loss of the Y chromosome. The loss of this chromosome acts as a biomarker for biological ageing that has been linked to age-related diseases, including Type 2 diabetes mellitus. Rare variants in the GIGYF1 gene were identified that significantly increase an individual’s risk of Y chromosome loss, subsequently increasing their risk of Type 2 diabetes mellitus six-fold.

Individuals carrying GIGYF1, which is believed to control insulin and cell growth factor signalling, were also seen to have other signs of widespread ageing, including muscle weakness and increased body fat. This genetic variant puts carriers at a 30% risk of developing Type 2 diabetes mellitus, compared to a 5% risk in the wider population.  “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,” revealed John Perry, senior author from the MRC Epidemiology Unit.

“Our findings highlight the exciting scientific potential of sequencing the genomes of very large numbers of people. We are confident that this approach will bring a rich new era of informative genetic discoveries that will help us better understand common diseases such as Type 2 diabetes,” explained Nick Wareham, Director of the MRC Epidemiology Unit. Scientists are continuing this research, with an aim to understand how the GIGYF1 variant leads to such an increase in susceptibility to Type 2 diabetes mellitus.