Recent studies have shown that mutation-intolerant genes capture much of the rare variant architecture of neurodevelopmental disorders such as autism, intellectual disability and developmental delay, as well as schizophrenia16–19. Here we show that, for schizophrenia, this also holds for common variation. Using gene set analysis in MAGMA20, loss-of-function (LoF)- intolerant genes (n = 3,230) as defined by the Exome Aggregation Consortium (ExAC)21 using their gene-level constraint metric (pLI ≥ 0.9), were enriched for common variant associations with schizophrenia in comparison with all other annotated genes (P = 4.1 × 10−16).
