Multi-trait genetic analysis identifies novel pleiotropic loci for depression and schizophrenia in East Asians

Abstract While genetic correlations, pleiotropic loci, and shared genetic mechanisms of psychiatric disorders have been extensively studied in European populations, the investigation of these factors in East Asian populations has been relatively limited. To identify novel pleiotropic risk loci for depression and schizophrenia (SCZ) in East Asians. We harnessed the most comprehensive dataset available for East Asians and quantified the genetic overlap between depression, SCZ, and their related traits via LD Score regression (LDSC) analyses. Besides the correlation between depression and SCZ, our analysis revealed significant genetic correlations between depression and obesity-related traits, such as weight, BMI, T2D, and HDL. In SCZ, significant correlations were detected with HDL, heart diseases and use of various medications. Conventional meta-analysis of depression and SCZ identified a novel locus at 1q25.2 in East Asians. Moreover, this locus was verified in the multi-trait analysis of GWAS (MTAG), which can improve the statistical power of single-trait GWAS by incorporating information from effect estimates across genetically correlated traits. Furthermore, multi-trait analysis of depression, SCZ and related traits identified ten novel pleiotropic loci for depression, and four for SCZ. Our findings demonstrate shared genetic underpinnings between depression and SCZ in East Asians, as well as their associated traits, providing novel candidate genes for the identification and prioritization of therapeutic targets specific to this population.