• Genetic risk for asthma comes from chang

    From ScienceDaily@1:317/3 to All on Mon Mar 28 22:30:42 2022
    Genetic risk for asthma comes from changes in airway cells, study finds


    Date:
    March 28, 2022
    Source:
    National Jewish Health
    Summary:
    A significant amount of genetic risk for asthma is likely mediated
    through altered gene expression within the airway epithelium. That
    is the conclusion of a new study to identify genetic variants that
    cause asthma by altering the function of airway cells.



    FULL STORY ==========================================================================
    A significant amount of genetic risk for asthma is likely mediated
    through altered gene expression within the airway epithelium. That
    is the conclusion of a National Jewish Health-led study to identify
    genetic variants that cause asthma by altering the function of airway
    cells. The team's paper published March 28, 2022, in the journal Nature Communications.


    ========================================================================== "This work will help us identify targetable pathways to intervene for
    asthma, to stop mucus hypersecretion or type 2 airway inflammation,
    an allergic response that can exacerbate asthma," said Max A. Seibold,
    PhD, professor of Pediatrics in the National Jewish Health Center for
    Genes, Environment and Health and senior author of the paper. "One of
    the banes of human existence is mucus, which plays a role in so many
    health conditions, everything from the common cold, to COVID, to chronic
    lung diseases like asthma and COPD. The more we know about what causes
    it, the better equipped we will be to develop impactful treatments."
    For the study, the team performed the first airway transcriptome-wide association study (TWAS) for childhood and adult onset asthma. The first
    step in a TWAS study is to build models that will allow prediction of how
    a person's genes will function in a particular tissue, based solely on
    their genetic profile. Dr. Seibold and colleagues leveraged nasal airway samples and genetic data from a cohort of 700 children in Puerto Rico,
    who either were in good health or had asthma, to build these models for
    airway tissue.

    The team then applied these models to genetic data from over 300,000 participants in the UK Biobank study, a large-scale biomedical database
    and research resource. This allowed them to test whether genetically
    altered function of airway genes is associated with asthma risk. The
    study data found over a third of identified genetic risk factors for
    asthma may confer their risk through alteration of the cells that line
    the airways (i.e. airway epithelium).

    In particular, the researchers found genetic changes in a gene that forms
    the structure of mucus (MUC5AC), and another gene (FOXA3) that directs
    the production of mucus secretory cells. This is one of the first times
    anyone has found genetic variants that influence asthma risk through the alteration of mucus secretory function. The team also found that some of
    the key genes in the type 2 inflammatory pathway have genetic changes that increase their level of expression in the airway, increasing asthma risk.

    This study was primarily funded by the National Heart, Lung, and
    Blood Institute (NHLBI). The Institute provides global leadership for
    research, training and education programs that promote the prevention
    and treatment of heart, lung, and blood diseases and enhance the health
    of all individuals so that they can live longer and more fulfilling
    lives. The NHLBI is one of the largest institutes within the National Institutes of Health (NIH).

    "This study demonstrates how obtaining additional data on the expression
    of genes from participants in genome-wide association studies can shed
    light on their biological functions. It also shows that some genes may
    be expressed differently in different tissues," said James P. Kiley,
    PhD, director of NHLBI's Division of Lung Diseases. "Research like this
    moves us one step closer to developing personalized medicine treatments
    for asthma and other common diseases." Asthma is a major health crisis
    in the United States. The Centers for Disease Control estimates 26.5
    million Americans, or 1 in 13 people, are living with the condition.


    ========================================================================== Story Source: Materials provided by National_Jewish_Health. Note:
    Content may be edited for style and length.


    ========================================================================== Journal Reference:
    1. Satria P. Sajuthi, Jamie L. Everman, Nathan D. Jackson, Benjamin
    Saef,
    Cydney L. Rios, Camille M. Moore, Angel C. Y. Mak, Celeste Eng, Ana
    Fairbanks-Mahnke, Sandra Salazar, Jennifer Elhawary, Scott Huntsman,
    Vivian Medina, Deborah A. Nickerson, Soren Germer, Michael C. Zody,
    Gonc,alo Abecasis, Hyun Min Kang, Kenneth M. Rice, Rajesh Kumar,
    Noah A.

    Zaitlen, Sam Oh, Jose' Rodri'guez-Santana, Esteban G. Burchard,
    Max A.

    Seibold. Nasal airway transcriptome-wide association study of
    asthma reveals genetically driven mucus pathobiology. Nature
    Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-28973-7 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/03/220328133631.htm

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