• Rare genetic variants confer largest inc

    From ScienceDaily@1:317/3 to All on Wed Jul 7 21:30:38 2021
    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)