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Oct. 30, 2015 Research Highlight Medicine / Disease

Global genes for gut disorders

People with inflammatory bowel disease share the same genetic risk factors the world over

Image of a woman with stomachache Figure 1: Inflammatory bowel disease is increasingly afflicting people of Asian ethnicity. © deeepblue/iStock/Thinkstock

The genetic regions that underlie susceptibility to inflammatory bowel disease (IBD) are almost the same in people of diverse ancestries around the world, a recent international study has found1. One implication of this finding is that drugs developed to target the genetic causes of the two forms of IBD—ulcerative colitis and Crohn’s disease—should prove effective for sufferers regardless of their ethnicity or genetic background.

“The basic mechanisms of IBD are common across populations,” says Atsushi Takahashi, a bioinformatics researcher at the RIKEN Center for Integrative Medical Sciences and a member of the International IBD Genetics Consortium that led the project. He added that since the mechanisms of other diseases are also shared across populations, international collaborations are important for developing insights into these diseases.

Unlike most previous investigations, which considered only individuals of one descent, the present study explored the genetic underpinnings of ulcerative colitis and Crohn’s disease in populations of four ancestries—East Asian, Indian, Iranian and European.

The researchers analyzed close to 200,000 DNA letters of each person from about 43,000 people with IBD and 53,500 healthy controls. Of these DNA samples, just under 10 per cent were from people of East Asian, Indian or Iranian descent, while the others were from people from Europe, North America and Oceania.

The results confirmed many genetic variants previously recognized as risk factors for IBD as well as revealing 38 regions of the genome that had not been implicated before. Of these newly identified regions, 27 were associated with both Crohn’s disease and ulcerative colitis, 7 with Crohn’s alone and 4 only with colitis.

Their findings bring the number of gene regions known to be linked to IBD to 200. Notably, the vast majority of the newly discovered gene regions were found in people with IBD from diverse ancestry groups. “Almost all the genes associated with IBD are shared between European and non-European populations,” Takahashi says.

With IBD increasing around the world—especially in Asia, where lifestyle changes brought about by economic growth have dramatically increased the incidence of these gut disorders—new treatments options are urgently needed.

The 38 new gene regions offer a range of potential avenues for drug development. Some genes are involved in cell degradation pathways, while others are responsible for activating specialized immune cells known as T cells. “Scientists can now investigate these gene loci in more detail, and new drugs may be developed,” Takahashi says.

References

  • 1. Liu, J. Z., van Sommeren, S., Huang, H., Ng, S. C., Alberts, R., Takahashi, A., Ripke, S., Lee, J. C., Jostins, L., Shah, T. et al. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nature Genetics 47, 979–986 (2015). doi: 10.1038/ng.3359

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