Results of functional genomics data analysis for pleiotropic vs. disorder-specific loci.(A) GTEX tissue-specific enrichment results for 146 risk loci associated with at least one of eight neuropsychiatric disorders. GTEX tissues were classified as 9 distinct categories, of which the brain tissues were colored in blue. The dotted red line indicates a statistically significant p-value after conducting Bonferroni correction for multiple testing. Psychiatric disorder-associated loci show significant enrichment in genes expressed in pituitary and all brain tissues except nerve_tibal. (B) Brain developmental expression trajectory displayed for the three groups of genes based on (Kang et al., 2011) The 146 genome-wide significant loci from the cross-disorder meta analysis were clustered into three groups based on predicted disorder-specific associations: (1) no-pleiotopy; (2) pleiotropy=2; and (3) pleiotropy>2. The “no-pleiotropy” group included 37 loci that showed a single-disorder-specific association, while the “pleiotropy=2” and “pleiotropy>2” groups included 60 and 49 loci that were associated with two and more than two disorders, respectively. (C) In the adult cortex, genes mapped to pleiotropic loci were enriched for frontal cortex specific genes, while genes mapped to non-pleiotropic loci are enriched for occipical cortex specific genes. (D) Genes mapped to 146 risk loci show higher expression values in neurons and oligodendrocytes, with much higher neuronal specificity for pleiotropic loci.
