Of the 109 risk loci with shared effects, the 18q21.2 region surrounding SNP rs8084351 at the netrin 1 receptor gene DCC featured the most pleiotropic association (Pmeta = 4.26 × 10−12; Fig. 3a). This region showed association with all eight psychiatric disorders, and has been previously associated with both MD and neuroticism (Turley et al., 2018; Wray et al., 2018). The signal in our meta-analysis colocalizes with brain eQTLs for DCC (eQTL association FDR q = 2.27 × 10−5), supporting DCC as a plausible candidate gene (Fig. S2). The product of DCC plays a key role in guiding axonal growth during neurodevelopment and serves as a master regulator of midline crossing and white matter projections (Bendriem and Ross, 2017). Gene expression data indicate that DCC expression peaks during early prenatal development (Fig. S3).
