Friday, 12 June 2015

Sharing MS Genes with other conditions

Fortune MD, Guo H, Burren O, Schofield E, Walker NM, Ban M, Sawcer SJ, Bowes J, Worthington J, Barton A, Eyre S, Todd JA, Wallace C. Statistical colocalization of genetic risk variants for related autoimmune diseases in the context of common controls.
Nat Genet. 2015 . doi: 10.1038/ng.3330. [Epub ahead of print]


Determining whether potential causal variants for related diseases are shared can identify overlapping aetiologies of multifactorial disorders. Colocalization methods disentangle shared and distinct causal variants. However, existing approaches require independent data sets. Here we extend two colocalization methods to allow for the shared-control design commonly used in comparison of genome-wide association study results across diseases. Our analysis of four autoimmune diseases-type 1 diabetes (T1D), rheumatoid arthritis, celiac disease and multiple sclerosis-identified 90 regions that were associated with at least one disease, 33 (37%) of which were associated with 2 or more disorders. Nevertheless, for 14 of these 33 shared regions, there was evidence that the causal variants differed. We identified new disease associations in 11 regions previously associated with one or more of the other 3 disorders. 

If we look at autoimmune diseases and read the papers about them there are common themes like T cells, MHC, Sex differences and it would expected that there would be common genetic pathways between diseases and this is what they found with some genes controlling susceptibility to different autoimmunities, others were different and others appeared to link with different variants, but this is not surprising anti-TNF makes arthritis better and MS worse.

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