Theres no doubt that inflammatory bowel disease is horrible. Its consequences, all sorts of gastrointestinal distress, can be downright debilitating. But treating it is full of uncertaintyfolks with the same symptoms might respond in wildly different ways. Thats why scientists are trying to pinpoint its cause, among all the genetic complexities that can contribute.
A team of researchers have made some fairly major progress in understanding, and hopefully treating, IBDs underlying causes, like Crohns disease and ulcerative colitis. They say theyve identified just a few dozen DNA base pairs, the As, Cs, Ts and Gs that spell out your genetic code, that could be responsible for causing the illness.
Inflammatory bowel disease, or IBD, is a disease with at least 1.4 million American sufferers that consists of a few underlying causes, like Crohns disease or ulcerative colitis, leading to inflammation in the digestive tract. It can lead to diarrhea and abdominal pain, as well as other unseen symptoms, according to the Mayo Clinic. The complex disease is probably not related to diet, but could be autoimmune.
Within IBD, there are common subtypes, study author Jeffrey Barrett from the Wellcome Trust Sanger Institute told Gizmodo. Some people respond to front line drugs and others dont... [Clinicians] want to give heavier hitting therapies, and dont want to give them to patients where they wont work. Were hoping this will help subdivide individual patient groups.
Scientists had already identified 200 base pairs that could be associated with IBD. But this time around, they analyzed the DNA of almost 68,000 people, including 34,000 healthy people, another 19,000 or so with Crohns disease and another 15,000 with ulcerative colitis. Through a painstaking statistical analysis, they were able to close in on just 18 key base pairs with over 95 percent certainty, and another 27 with over a 50 percent certainty. These letters affect the way specific proteins look, places where proteins bind to DNA, and other changes in some immune cells associated with IBD. The team published their results yesterday in the journal Nature.
If this information seems a little esoteric, thats okayit wont directly lead to treatment, yet. Instead, its important for developing new IBD drugs, Barrett said. He leads a program called Open Targets that collaborates with the European Bioinformatics Institute and drug companies like GSK. The idea is to hand these findings off to scientists in the drug companies and say these are the proteins or signaling pathways that are most important for IBD, and the ones you should go after with new drugs.
One researcher not involved with the study, Michael Helmrath, surgical director of the Intestinal Rehabilitation Center at Cincinnati Childrens Hospital, agreed the study may be of interest due to how common IBD is. But how exactly the information would be used by scientists developing treatments, he is still unclear on.
And Mark Daly, study author and Chief of the Analytic and Translational Genetics Unit at Mass General Hospital told Gizmodo in an email that weve still got a long way to go before interpreting what these variations in the genome actually mean. Just because things are different between people with and without IBD doesnt necessarily mean scientists have made a real biological insight, he said. There are other limitations, toothe sequenced genomes all came from Europeans, leaving out folks from the rest of the globe. This means that they might miss some other IBD-causing variations due to the presence of other differences in the genome between people, said Barrett.
But that doesnt mean the work isnt importantit has huge implications for the future of studying complex genetic diseases.Here weve shown that genetic studies done at large scale and extremely high resolution can often implicate one or a small number of variants at the root of the genomic-wide association study associations, and thereby advance the conversion of these findings towards biological insight, Daly said.
More specifically, Barrett hopes that studies like these can one day help scientists understand complex chronic diseases like diabetes and schizophrenia. In these cases, scientists have found general genetic associations. But big studies can help drill into the specific causes. He said: This will serve as the basis of how new biology [insights] might be informative for looking at new drugs.
[Nature]
Link:
Enormous Genetic Study Will Help Scientists Treat Inflammatory Bowel Disease - Gizmodo
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