Rare genetic variants confer largest increase in typediabetes risk
seen to date
Date:
July 7, 2021
Source:
University of Cambridge
Summary:
Scientists have identified rare genetic variants - carried by one in
3,000 people - that have a larger impact on the risk of developing
type 2 diabetes than any previously identified genetic effect.
FULL STORY ========================================================================== Scientists at the University of Cambridge have identified rare genetic
variants -- carried by one in 3,000 people -- that have a larger impact
on the risk of developing type 2 diabetes than any previously identified genetic effect.
==========================================================================
Type 2 diabetes is thought to be driven in part by inherited genetic
factors, but many of these genes are yet unknown. Previous large-scale
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. Proteins are essential molecules that
enable our bodies to function. In particular, this new approach has
allowed for the first time a large-scale approach to study the impact
of rare genetic variants on several diseases, including type 2 diabetes.
By looking at data from more than 200,000 adults in the UK Biobank study, researchers from the Medical Research Council (MRC) Epidemiology Unit
at the University of Cambridge used this approach to identify genetic
variants associated with the loss of the Y chromosome. This is a known biomarker of biological ageing 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 previously linked to age-related diseases such
as type 2 diabetes and cancer.
In results published today in Nature Communications, the researchers
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 associated with type 2 diabetes confer much more modest increases in risk, typically much lower than two-fold.
Around 1 in 3,000 individuals carries 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 ageing, including weaker muscle
strength and more body fat.
GIGYF1 is thought to control insulin and cell growth factor
signalling. The researchers say their findings identify this as a
potential target for future studies to understand the common links
between metabolic and cellular ageing, and to inform future treatments.
Dr John Perry, from the MRC Epidemiology Unit and a senior author
on the paper, said: "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." Professor Nick Wareham, Director of the MRC Epidemiology Unit, added:
"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. By doing this, we can potentially offer better ways to treat
-- or even to prevent -- the condition." Ongoing research will aim to understand how the loss of function variants in GIGYF1 lead 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 ageing in adults and metabolic disorders.
========================================================================== Story Source: Materials provided by University_of_Cambridge. The original
story is licensed under a Creative_Commons_License. Note: Content may
be edited for style and length.
========================================================================== Journal Reference:
1. Yajie Zhao, Stasa Stankovic, Mine Koprulu, Eleanor Wheeler, Felix
R. Day,
Hana Lango Allen, Nicola D. Kerrison, Maik Pietzner, Po-Ru
Loh, Nicholas J. Wareham, Claudia Langenberg, Ken K. Ong, John
R. B. Perry. GIGYF1 loss of function is associated with clonal
mosaicism and adverse metabolic health. Nature Communications,
2021; 12 (1) DOI: 10.1038/s41467-021- 24504-y ==========================================================================
Link to news story:
https://www.sciencedaily.com/releases/2021/07/210707112530.htm
--- up 8 weeks, 5 days, 22 hours, 45 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)