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The role of polygenic risk score gene-set analysis in the context of the omnigenic model of schizophrenia rdcu.be/bBhtM - new paper from my grad student Alexandros Rammos and our collaborators, including co-supervisor Kristin Nicodemus 
Given the omnigenic model (which suggests ALL genes expressed in the brain should harbor some genetic variants contributing to risk of schizophrenia) we ask whether any particular gene sets explain more of the variance than others
We do indeed find that some sets - derived from interactions with "anchor" genes like TCF4, FMR1... - capture more of the variance than expected (and develop a method to quantify that beyond just demonstrating enrichment)
However, the enrichment is not huge and the existence of a floor effect for non-selected genes does support the idea of very widespread contributions to the proportion of variance captured by common variants
There is thus a limit on how far we will be able to highlight major biochemical or genetic pathways underlying schizophrenia, as there probably aren't any
