Conditional False Discovery Ratewas Used To Identify Polytropic Genetic Loci Of Major Depressive Disorders And Anxiety Disorder

Objective: In order to provide clues for the study of the common genetic basis and pathogenesis of major depressive disorders and anxiety disorders,the recent published data of Genome-wide Association Study(GWAS)on major depressive disorders and anxiety disorders published in large-scale European population were analyzed to identify the common susceptible loci of the two diseases.Method: The public GWAS data downloaded from the official website of the Psychiatric Genomics Consortium and the Integrative Psychiatric Research were analyzed in the way of conditional false discovery rate(condFDR)under the condition of major depressive disorders and anxiety disorders respectively to identify susceptible loci or genes of the two disorders.Then stratified conditional quantile figure was applied to calculate the enrichment degree of pleiotropic loci between major depressive disorders and anxiety disorders with the statistical analysis method of conjunction false discovery rate(conjFDR).And the methods of genome annotation and pathway analysis were adopted for further acquaintance of the biological function of the susceptible loci or genes.Results:1.The stratified conditional quantile figure and conditional enrichment figure showed significant genetic pleiotropic enrichment between major depressive disorders and anxiety disorders.2.Conditional false discovery rate analysis showed that a total of 32 susceptible loci were identified to be significantly associated with major depressive disorders under the significant threshold of condFDR<0.01,including 30 new genetic variation sites.The results of pathway enrichment analysis showed that these susceptible loci were enriched in synaptic transmission related pathways including 7 pathways such as“resynapse organization”(GO:0099172;FDR =2.18E-03),“synapse organization”(GO:0050808;FDR =6.00E-03),“cell adhesion molecule binding ”(GO:0050839;FDR =8.02E-03),“membrane biogenesis”(GO:0044091;FDR =2.79E-02),et al.Meanwhile,7 newly genetic variation loci were significantly associated with anxiety disorders.3.37 genetic pleiotropy loci associated with major depressive disorders and anxiety disorders were identified with conjFDR< 0.05 as the significant threshold.The results of pathway enrichment analysis showed that these susceptible loci were enriched in synaptic transmission related pathways including 9 pathways such as “ dendritic spine ”(GO:000043197;FDR =2.09E-02),“ transmembrane transporter complex”(GO:1902495;FDR =3.99E-02),et al.Conclusion:Based on the condFDR and conjFDR analysis,significant pleiotropy enrichment between major depressive disorders and anxiety disorders was detected.30 variation loci associated with major depressive disorders and7 variation loci associated with anxiety disorders were newly identified by the method of condFDR analysis.37 newly discovered genetic pleiotropy loci identified by conjFDR analysis involving 9 biological pathways mainly enriched in synaptic-related pathways,which indicated some potential common genetic mechanisms between the two disorders.This result provided important clues and scientific basis for the study of the common genetic and pathological mechanism of major depressive disorders and anxiety disorders.