Next, we performed an agnostic search for overlap between our schizophrenia-associated genes and ~ 8,500 molecular pathways collated from large, publicly available databases. Thirty-three pathways were significantly enriched after FDR correction (Table 2, Suppl. Table 2), including a number of pathways with some prior literature in psychiatric disease. We identified an enrichment with porphyrin metabolism (p = 1.03 × 10−4). Deficiencies in porphyrin metabolism lead to “Porphyria”, an adult-onset metabolic disorder with a host of associated psychiatric symptoms, in particular episodes of violence and psychosis33-38. Five pathways potentially related to porphyrin metabolism, regarding abnormal iron level in the spleen, liver and kidney are also significantly enriched, including 2/5 of the most highly enriched pathways (p < 2.0 × 10−4). The PANTHER and REACTOME pathways for Heme biosynthesis and the GO pathway for protoporphyrinogen IX metabolic process, which are implicated in the development of porphyric disorders, are also highly enriched (p = 2.2 × 10−4, 2.6 × 10−4, 4.1 × 10−4), although do not pass FDR-correction.
