| Background Major depressive disorders and insomnia disorders are often coexit, which have some common pathogenesis and may be regulated by the same pleiotropic genes. Previous GWAS studies generally used single-trait studies, which have certain limitations in explaining gene pleiotropic effects. Objective we aimed to examine whether major depressive disorders and insomnia disorders share genetic risk factors utilizing recent large-scale genome-wide association studies (GWAS). Methods The genome-wide association study （GWAS） data sets were downloaded from the Psychiatric Genomics Consortium(PGC) and Sleep Disorder Knowledge Portal. The major depressive disorders related GWAS data including 561 190 controls and 246 363 cases, and the insomnia disorders related GWAS data involving 1 331 010 subjects. the cFDR and ccFDR were used to identify pleiotropic genetic loci significantly associated with major depressive disorders and insomnia disorders. we used path enrichment analysis to further determine the biological functions of the susceptibility sites. Results There was significant genetic pleiotropic enrichment between major depressive disorders and insomnia disorders. Leveraging this enrichment, A total of 21 susceptibility loci and major depressive disorders were identified in this study with a significance threshold of cFDR<0.01, including 17 new genetic variation loci. At the same time, 38 genetic variation loci were identified with significant associations with insomnia disorders, including 28 newly discovered susceptibility loci. The ccFDR analysis identified 16 independent pleiotropic SNPs for both major depressive disorders and insomnia disorders(ccFDR<0.05), 15 of which were newly discovered. Pathway enrichment analysis showed that the enrichment of susceptibility loci associated with synaptic transmission, Such as postsynaptic density (GO:0014069; P=4.91E-04; FDR=4.84E-03), asymmetric synapse(GO:0032279; P=5.09E-04; FDR=4.84E-03), regulation of postsynaptic membrane neurotransmitter receptor levels(GO:0099072; P=5.11E-04; FDR=1.69E-02) .Conclusion Our study found that there was a significant pleiotropic enrichment between major depressive disorders and insomnia disorders, and the comorbidity mechanism was related to synaptic transmission. |