Largest genetic study of inflammatory bowel disease provides clues on new drug targets

Scientists identify genetic variant that doubles
an individual's risk of developing ulcerative
colitis
January 30, 2017
Wellcome Trust Sanger Institute
Medical researchers have
identified a genetic variant that
doubles an individual's risk of
developing ulcerative colitis,
one of the subtypes of a chronic
disorder known as Inflammatory
Bowel Disease (IBD).
Cite This Page:
Wellcome Trust Sanger Institute. "Largest
genetic study of inflammatory bowel disease
provides clues on new drug targets: Scientists
identify genetic variant that doubles an
individual's risk of developing ulcerative colitis."
ScienceDaily. ScienceDaily, 30 January 2017.
<www.sciencedaily.com/
releases/2017/01/170130092056.htm>.
FULL STORY
In two studies published today (30 January) in
Nature Genetics, researchers from the Wellcome
Trust Sanger Institute and their collaborators
have identified a genetic variant that doubles an
individual's risk of developing ulcerative colitis,
one of the subtypes of a chronic disorder known
as Inflammatory Bowel Disease (IBD).
They also uncover a further 25 novel genetic
associations to IBD risk, including several that
implicate genes related to a class of
therapeutics that has shown promise in the
treatment of this disease.
More than 300,000 people suffer from IBD in the
UK. The disorder primarily consists of two
subtypes: ulcerative colitis and Crohn's disease,
neither of which currently have a cure. IBD is a
debilitating disease in which the body's own
immune system attacks parts of the digestive
tract. The exact causes of this disease are
unclear.
To understand more about the genetics
underlying IBD, researchers studied the
genomes of 16,000 UK IBD patients, as well as
10,000 more from a previously published
international study, in the largest whole-genome
IBD genetic study to date.
From the research, which included 5 per cent of
IBD sufferers nationwide, scientists identified a
rare genetic variant that doubles the risk of
ulcerative colitis. The variant affects a gene
known as ADCY7, and is carried by 1 in 200
people in the UK. It is one of the strongest
genetic risk factors associated with ulcerative
colitis to date and presents a novel drug target
for IBD.
In the second study, researchers identified that a
family of proteins called integrins play a key role
in increasing the risk of IBD. Integrins are
transmembrane proteins that act as bridges for
interactions between cells from the immune
system and the rest of the body. For the
inflammation associated with IBD symptoms,
drugs targeting some of these interactions have
been shown to be effective. This study
demonstrated that genetic variants that increase
the risk of developing IBD also increase the
expression of certain integrins in response to
stimulation of the immune system.
Katrina de Lange, first author from the Wellcome
Trust Sanger Institute, said: "We study genetics
because we ultimately want to understand the
biology of the disease. From the genetic
information we can extract a compelling story
about why a particular anti-integrin drug is
effective against Inflammatory Bowel Disease, or
why others have serious side effects."
These examples of genome wide association
studies give scientists a clearer view of IBD
biology than they had previously and are helping
to reveal the underpinning biology of human
inflammatory diseases overall.
Looking to the future, Sanger Institute scientists,
with help from the UK IBD BioResource, are
aiming to sequence 25,000 genomes of IBD
patients in the next five years. The
unprecedented scale of this study will hopefully
reveal even more details of the biology of this
condition.
Dr Miles Parkes, co-author of the studies and
consultant gastroenterologist at Addenbrooke's
Hospital in Cambridge, said: "Whilst there are
challenges in recruiting large numbers of
patients to IBD studies and interpreting the
resulting volume of data, there are also great
opportunities to better understand the role of
genetic variation in not only risk of disease but
also in treatment and prognosis. The IBD
Bioresource will drive recruitment of IBD
patients across the UK and allow recall of
patients for repeat tests so the function of
specific genes behind IBD can be explored."
The results from these studies will be translated
into potential treatments by Open Targets, an
initiative that takes the outputs of the genetic
studies and works with pharmaceutical
companies to aid the development of new
treatments for diseases including IBD.
Dr Carl Anderson, a lead author from the
Wellcome Trust Sanger Institute said: "The scale
of these collaborations means we are able to
spot genetic associations to IBD that we hadn't
seen previously. We hope that by continuing to
work together we will be able to translate these
findings into better treatments for IBD patients."
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