Cotsapas et al. Pervasive Sharing of Genetic Effects in Autoimmune Disease. PLoS Genet. 2011 Aug;7(8):e1002254.
Genome studies have identified numerous genetic associations between common genetic variants (small changes in the DNA code) and risk of other autoimmune diseases; some of these genetic variants are shared between two diseases.
Along with clinical evidence, this suggests that some genetic risk factors may be shared across several diseases.
In this study the investigators evaluated the extent of this sharing for 107 immune disease-risk variants in seven diseases: celiac disease (gluten sensitivity), Crohn’s disease (inflammatory bowel disease), MS, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes.
They found evidence that 47/107 (44%) immune-mediated disease risk variants are associated with multiple, but not all-immune-mediated diseases.
They also showed that distinct groups of interacting proteins are encoded near these variants in our genomes, which predispose to the same subsets of diseases.
They propose that common genetic risks and mechanisms underlie several related autoimmune diseases. The mechanisms are inferred from the proteins that occur near these genetic variants.
“Why is this important?”
“It may provide us with clues to the cause of MS and provide common treatment targets for several diseases. If we can identify an important pathway common to several disease we may be able to design a drug to target this pathway.”
“Please let me know if this post is easier to understand than yesterday’s on immunology?”
“This paper is a theoretical paper based on data already published. The term we use for this type of analysis is ‘in silico’; i.e. data mining done a computer. What this paper needs is some hard core lab work on MS’ers and control samples to see if these variants have functional consequences on the way their immune systems function.”
Additional reading: celiac disease, Crohn’s disease, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and type 1 diabetes.
Thanks G.Just to be clear, does that mean that PwMS are at a higher risk (due to genetic profile) to suffer from other imuno-related diseases?If so, should PwMS be on the watch for IBD, Gluten….Thanks again.
Re: "Just to be clear, does that mean that PwMS are at a higher risk (due to genetic profile) to suffer from other imuno-related diseases?"No, people with these genetic variants are more likely to get auto-immune disease. The evidence that MS'ers are more prone to get other autoimmune diseases is weak. Studies reporting an association are probably biased.
What i understood is- – 56% of these gene variants are associated with just 1 of these 7 diseases. If they had included other diseases in the study they might have found more associations- Scientists need to find the process by which having a gene variant leads to having the disease. They expect parts of the process to be common across associated diseasesthere are many news reports about the discivery of a link between a gene and a disease. Have these findings led to anything useful yet? with just 1 of these 7 diseases. If they had included other diseases in the study they might have found more associations- Scientists need to find the process by which having a gene variant leads to having the disease. They expect parts of the process to be common across associated diseasesthere are many news reports about the discivery of a link between a gene and a disease. Have these findings led to anything useful yet?
The gene studies are only just bearing fruit and it is too ealry to say how useful these studies have or will be.Scientists may already know how a variant of one gene may contribute to disease susceptibility. However, but just because we know that a gene causes disease, does not mean that we can or should do anything about it, at presentDealing with a single gene disease is a problem. Dealing with a disease, such as MS, caused by tens-hundreds of genes is an even taller order. This is further complicated by the liklihood that not everybody with MS will have the same set of these gene variants. Furthermore just because you have them does not mean that you will get MS.The genetic cause of sickle cell anaemia, Huntingtons disease and thalessemia are all caused by single gene effects and this has been known for years. However, we do not yet have treatments. In some cases there may be treatments such as with bubble babies.The gene causing the main genetic association with MS has been known for over thirty years. However, it is a perfectly normal gene, just as the other genes that will associate with MS and other autoimmune diseases will be. Therefore, interefering with them individually may not be the solution.These genes will have been selected to help protect human population from infections, but the down side at the individual level is that some people will get autoimmunity. This is why some genes will be common across different disease, because many of the disease processes are the same.How these genetic variants intereact will be a key part of our understanding and who knows they may lead to treatments in the future.