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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