Fig. 1

Overview of investigation of the impact of common and rare variation in retinoid genes. Using gene ontology and the wider literature, a panel of 107 genes involved with retinoid biology were collated and tested for the aggregated effect of GWAS SNPs using MAGMA. An uncorrected threshold of P < 0.05 was used to delineate genes with evidence of a polygenic effect. Polygenic risk score (PRS) was then calculated in individuals for this retinoid panel. Retinoid PRS was associated with schizophrenia but did not disproportionately affect the cognitive deficit (CD) subtype. Rare variant association (MAF < 0.01%) from whole-genome sequencing was tested at gene level for each of the 22 genes using the SKAT-O framework. The retinoic acid receptor gene RARB was significantly associated with the CD population, but there were no significant gene level signals for the full case cohort (cognitively mixed) relative to controls