Scientists from the University of Cambridge found rare genetic variants that have a larger impact on the risk of developing type 2 diabetes than any previously identified genetic effect.
The research is published in Nature Communications and was conducted by John Perry et al.
Type 2 diabetes is thought to be driven in part by inherited genetic factors, but many of these genes are yet unknown.
Previous studies have depended on efficient ‘array genotyping’ methods to measure genetic variations across the whole genome.
This approach typically does a good job at capturing the common genetic differences between people, though individually these each confer only small increases in diabetes risk.
Recent technical advances have allowed more comprehensive genetic measurement by reading the complete DNA sequences of over 20,000 genes that code for proteins in humans.
In the study, the researchers used data from more than 200,000 adults in the UK Biobank study. They identified genetic variants associated with the loss of the Y chromosome.
This is a known biomarker of biological aging that occurs in a small proportion of circulating white blood cells in men and indicates a weakening in the body’s cellular repair systems.
This biomarker has been linked to age-related diseases such as type 2 diabetes and cancer.
The team identified rare variants in the gene GIGYF1 that substantially increase susceptibility to loss of the Y chromosome, and also increase an individual’s risk of developing type 2 diabetes six-fold.
In contrast, common variants linked to type 2 diabetes confer much more modest increases in risk, typically much lower than two-fold.
Around 1 in 3,000 individuals carry such a GIGYF1 genetic variant. Their risk of developing type 2 diabetes is around 30%, compared to around 5% in the wider population.
In addition, people who carried these variants had other signs of more widespread aging, including weaker muscle strength and more body fat.
The researchers suggest that these findings found a potential target for future studies to understand the common links between metabolic and cellular aging, and to inform future treatments.
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