Of the 109 pleiotropic loci, 76 were identified in the GWAS of individual disorders, while the remaining 33 are novel. The most pleiotropic among these novel loci was a region downstream of NOX4 (NADPH Oxidase 4) that was associated with SCZ, BIP, MD, ASD, and AN (rs117956829; Pmeta = 1.82 × 10−9; Fig. 3c). Brain Hi-C data (Wang et al., 2018; Won et al., 2016) detected a direct interaction of the cross-disorder association region with NOX4 in both adult and fetal brain (interaction p=3.2×10−16 and 9.3×10−6, respectively). As a member of the family of NOX genes that encode subunits of NADPH oxidase, NOX4 is a major source of superoxide production in human brain and a promoter of neural stem cell growth (Kuroda et al., 2014; Topchiy et al., 2013).
