Assessing multiple associations in autoimmunity

Single nucleotide polymorphisms (SNPs) and/or point mutations have been a recurrent theme throughout various research on autism spectrum and lots of other conditions in recent times. The accumulated data on the subject seems to indicate several things: (i) we are all a product of mutation (whether we have autism or not), (ii) there are multiple mutations suggested to be linked to autism, although so far no one 'pattern' of mutation showing universal consistency, and (iii) the underlying reason why such mutations occur has not yet been elucidated although one would strongly suspect some role for 'environment', whatever that is taken to mean.

I say all this because a recent paper by Cotsapas and colleagues* published in the journal PLoS Genetics exemplifies SNPs in action and offers some new data on how shared SNPs across various conditions might indicate some shared effects particularly in some cases of autoimmune disease. The paper which is open-access looked at various conditions with an autoimmune component attached. This included: coeliac (celiac) disease, inflammatory bowel disease and type-1 diabetes; conditions which have been covered to varying degrees as being comorbid to some cases of autism.

Their findings based on some statistical wizardry, the cross phenotype meta-analysis, suggested that over 40% of the SNPs identified were associated with 'multiple but not all' immune mediated diseases. Interestingly they also summarised various interacting proteins encoded by the genes roundabout the identified SNPs which might implicate some shared disease risk. IL-12b and IL-23R were mentioned specifically.

I find this article to be an interesting one. It is fairly well known that your risk of developing an autoimmune condition is enhanced if you happen to suffer with one already. For example, those with type-1 diabetes are at greater risk of coeliac disease; something which a sister blogpost covered recently. Those with psoriasis are at greater risk of rheumatoid arthritis. The bonus value of the current paper is the way they approached the analysis of SNPs isolated in these autoimmune conditions in their analysis - 'assessing multiple associations to a marker'.

* Cotsapas C. et al. Pervasive sharing of genetic effects in autoimmune disease. PLoS Genetics. August 2011.