Identification of 1q25.2 as a novel shared locus between schizophrenia and major depressive disorder in east Asians by integrative analyses.

Schizophrenia (SZ) and major depressive disorder (MDD) share psychopathological features, and their overlapped genetic architectures have been well-studied in Europeans. However, the extent of their polygenic overlap in East Asians remains unclear. Genome-wide association study (GWAS) datasets present a valuable resource for exploring this question. We applied linkage disequilibrium score (LDSC) regression and MiXeR analyses to assess polygenic overlap. Cross-trait meta-analysis was used to identify shared genomic loci between disorders. Expression quantitative trait loci (eQTL) and diagnostic analyses of mRNA expression were utilized to localize risk gene(s). Using GWAS datasets of SZ (29,519 cases and 44,392 controls) and MDD (7753 cases and 14,046 controls), we conducted LDSC regression and MiXeR analyses, revealing substantial genetic overlap between the two disorders. Genome-wide meta-analysis highlighted a novel risk locus at 1q25.2. The risk SNPs at this locus showed significant eQTL associations with FAM20B mRNA expression across the brain and blood, consistent with higher gene expression observed in cases. We highlighted a novel genome-wide risk locus in East Asians linked to SZ and MDD, reinforcing evidence for their shared genetic overlap. Our study emphasizes the significance of mining public datasets to explore psychiatric risk genes.