Gene variations at birth reveal origins of inflammation and immune
disease

Date:
July 28, 2020
Source:
Baker Heart and Diabetes Institute
Summary:
A study has pinpointed a number of areas of the human genome
that may help explain the neonatal origins of chronic immune and
inflammatory diseases of later life, including type 1 diabetes,
rheumatoid arthritis and celiac disease.



FULL STORY ==========================================================================
A study published in the journal Nature Communications has pinpointed a
number of areas of the human genome that may help explain the neonatal
origins of chronic immune and inflammatory diseases of later life,
including type 1 diabetes, rheumatoid arthritis and celiac disease.


==========================================================================
The research, led by scientists at the Cambridge Baker Systems Genomics Initiative, identified several genes that appear to drive disease risk
at birth, and which could be targeted for therapeutic intervention to
stop these diseases in their tracks, well before symptoms occur.

Dr Michael Inouye, Munz Chair of Cardiovascular Prediction and Prevention
at the Baker Institute and Principal Researcher at Cambridge University,
said chronic immune and inflammatory diseases of adulthood often
originated in early childhood, with an individual's genetic make-up
causing changes to the function of different genes involved in disease.

For this study, the team collected cord blood samples from more than
100 Australian newborns as part of the Childhood Asthma Study, and
investigated the role of genetic variation in DNA in changing how genes
are expressed in the two main arms of the immune system.

The neonatal immune cells were exposed to certain stimuli, to see how
the cells responded and to identify genetic variants that changed these responses.

"We looked for overlap between these genetic signals and those that are
known to be associated with diseases where we know the immune system
plays a role," Dr Inouye said.



==========================================================================
"We then used statistical analysis to search for possible links between
the cell response in newborns and immune diseases in adulthood." Chronic immune diseases -- including type 1 diabetes, celiac disease and multiple sclerosis -- are caused by an overactive immune system and affect about
5 per cent of Australians. Allergies are immune-mediated too and affect
one in five Australians, with hay fever, asthma, eczema, anaphylaxis and
food allergies the most common. Inflammation and autoimmunity are also
known to be driving factors in cardiovascular diseases, for example when
an overactive immune system mistakenly attacks the heart.

Dr Qinqin Huang, lead author of the study and now a researcher at the
Wellcome Sanger Institute in Cambridge, said the findings were unique in
their scale, with thousands of genetic variants driving gene expression
across different immune and inflammatory conditions, some of which had wide-ranging effects.

"Our study showed the potential roles of gene expression in disease development, which has helped us to better understand the link between
DNA variation and disease risk," Dr Huang said.

"To date, similar studies have only been conducted in adult immune
cells. Given the huge difference between neonatal and adult immunity,
it is not surprising to see many signals that were unique to newborns."
The study is part of the Cambridge Baker Systems Genomics Initiative's
wider work in developing polygenic risk scores to predict an individual's likelihood of developing particular chronic diseases. To date, the team
have already developed potential methods to test for future risk of
stroke and coronary artery disease.



========================================================================== "Disease is partly due to changes, both large and small, in our genome --
the DNA that we're born with and which is a major driving force in all
our cells.

That means, genomics can be used to estimate disease risk from a very
early age," Dr Inouye said.

"Common diseases, such as type 2 diabetes and cardiovascular disease,
tend to be polygenic -- influenced by a large number of genetic variants scattered throughout the genome, which combine with environmental and
lifestyle factors.

By using new genomic technology and supercomputing capabilities, we can
sift through this DNA data and piece together the puzzles that underlie
each disease.

"With so many diseases sharing a root in the immune system and
inflammation we can leverage this information to better understand
where each disease has a molecular weak spot and to what extent these
are shared among different diseases.

"We've shown this can be dissected using genetics and polygenic risk,
hopefully leading to targeted preventative interventions for those
who need them most, with the aim of keeping people living healthier
for longer."

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


========================================================================== Journal Reference:
1. Qin Qin Huang, Howard H. F. Tang, Shu Mei Teo, Danny Mok, Scott C.

Ritchie, Artika P. Nath, Marta Brozynska, Agus Salim, Andrew
Bakshi, Barbara J. Holt, Chiea Chuen Khor, Peter D. Sly, Patrick
G. Holt, Kathryn E. Holt, Michael Inouye. Neonatal genetics
of gene expression reveal potential origins of autoimmune and
allergic disease risk. Nature Communications, 2020; 11 (1) DOI:
10.1038/s41467-020-17477-x ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200728113550.htm

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