We identified three significantly associated pathways in our hypothesis-driven analysis (Table 2). Targets of the fragile-X mental retardation protein formed the most enriched pathway (FMRP; p = 1.96 × 10−8). Loss of FMRP inhibits synaptic function, is comorbid with autism spectrum disorder, and causes intellectual disability, as well as psychiatric symptoms including anxiety, hyperactivity and social deficits27. Enrichment of this large group of genes has been observed frequently in studies of schizophrenia28,29 and autism27,30. There was a significant enrichment among our SCZ-associated genes and genes that have been shown to be intolerant to loss-of-function mutations31 (p = 5.86 × 10−5) as well as with copy number variants (CNVs) associated with bipolar disorder32 (p = 7.92 × 10−8), in line with a recent GWAS study of the same individuals29.
