The "omnigenic" model for schizophrenia - why it's even worse than you think.
I'm happy to see the article by Boyle, Yang and Pritchard (Boyle et al, 2017) getting so much attention. Quite justifiably, many people are commenting on it and I thought I would add my two pence worth. To summarise, I think the main claim they are making is that for a complex disease there will be a relatively small number of "core" genes whose functioning is related to disease mechanisms but that a very large number of polymorphisms will impact to a small extent on these core genes through gene expression networks. This then leads to a phenomenon whereby GWAS hits are very widely scattered through the genome. Most of these hits will not be anywhere near genes involved in disease mechanisms, they'll just reflect impacts on generic expression networks in one way or another. Here, I'd like to add another dimension, taking schizophrenia as an example. My claim will be that as well as the core genes there will be many other genes which do have an effect on risk,