The first genetic study of inflammatory bowel disease (IBD) to
include individuals from diverse populations has shown that the
regions of the genome underlying the disease are consistent around
the world.
This study, conducted under the auspices of the International
IBD Genetics Consortium, included nearly 10,000 DNA samples from
people of East Asian, Indian or Iranian descent and an existing set
of 86,640 samples drawn from across Europe, North America and
Oceania.
The observation that genetic effects on disease risk are
consistent across diverse populations is an important one because
it suggests that the biology underlying disease is also consistent.
This could have profound consequences for the treatment of IBD
because drugs developed based on insights from genetic studies in
one population could be used worldwide.
"The prevalence of IBD has increased dramatically in Asia over
the last 50 years, probably due to lifestyle changes brought about
by economic growth," says Dr Carl Anderson of the Wellcome Trust
Sanger Institute. "We are now able to compare genetic risk profiles
of IBD across diverse populations to find out how similar they are.
Discovering differences can provide us with biological insights
that would be missed if we were to focus our efforts on just a
single population. In turn, this can lead to the identification of
new drug targets."
"In our study we found little difference in the genetic risk of
IBD across the populations we studied. This is a very important
finding because it suggests that biological lessons learned by
studying the genetics of IBD will be relevant globally."
More than 163 variants in the human genome have already been
associated with increased risk of IBD, the most common forms of
which are Crohn's disease and ulcerative colitis, but this research
has only been conducted at a large scale in Europeans.
By including 10,000 non-European samples alongside the existing
European samples, the team were able to detect 38 additional
regions of the genome that influence susceptibility to IBD. Because
the genetic effects were largely consistent across populations, the
researchers hypothesized that the reason they were able to discover
these new regions was the big increase in sample size, rather than
because the additional samples were drawn from non-European
individuals.
"We've already seen the benefit of using trans-ethnic approaches
to understand complex diseases such as type 2 diabetes and
rheumatoid arthritis," says Dr Jimmy Liu, also from the Sanger
Institute. "This study demonstrates the importance of collecting
trans-ethnic data on IBD, firstly because any increase in the
number of samples improves our ability identify regions of the
genome influencing disease risk, and secondly because we can gain
new insights into the biology underlying IBD by comparing results
across the diverse populations."
Despite the wide-spread similarities, the study did confirm
previously identified differences between IBD risk in European and
non-Europeans. There are genetic variants in a gene called NOD2
which increase risk of IBD in Europeans that are simply not present
in Asian populations. It remains to be seen if there are IBD
risk-increasing variants in NOD2 that are only present in Asia. At
another gene, called TNFSF15, the IBD risk-increasing variants are
at a similar frequency in both Europeans and East Asians, but the
variants seem to have a much stronger effect on disease risk in
East Asia. The team have suggested this finding could be due to
subtle differences in the environment or genome structure.
"This study is testimony to the need for large-scale
international collaborations that enable us to answer questions
that would not be possible using samples drawn from a single
population," says Dr Rinse K Weersma, of University Medical Center
Groningen. "We thank every individual who donated a DNA sample to
the study and the clinicians within the International IBD Genetics
Consortium who collected these, particularly those outside of the
US and Europe.
"The finding that the biology underlying IBD is consistent
across populations is hugely important, it tells us that we can use
insights from genetic studies of IBD to develop globally relevant
drugs with the potential to improve disease management around the
world."
The paper, Association analyses identify 38 susceptibility loci for
inflammatory bowel disease and highlight shared genetic risk across
populations, is published in Nature
Genetics.