Novel loci and potential mechanisms of major depressive disorder,bipolar disorder,and schizophrenia

作     者：He Wang Zhenghui Yi Tieliu Shi He Wang;Zhenghui Yi;Tieliu Shi

作者机构：Center for Bioinformatics and Computational BiologyInstitute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghai 200030China Key Laboratory of Advanced Theory and Application in Statistics and Data Science-MOESchool of StatisticsEast China Normal UniversityShanghai 200062China Beijing Advanced Innovation Center for Big Data-Based Precision MedicineBeihang University&Capital Medical UniversityBeijing 100083China 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2022年第65卷第1期

页      面：167-183页

核心收录：

学科分类：1002[医学-临床医学] 100205[医学-精神病与精神卫生学] 10[医学] 

基　　金：supported by the National Key Research and Development Program of China(2015AA020108) the National Natural Science Foundation of China(31671377,81671326) Shanghai Municipal Science and Technology Major Project(2017SHZDZX01) Open Research Fund of Key Laboratory of Advanced Theory and Application in Statistics and Data Science(East China Normal University)of Ministry of Education the Fundamental Research Funds for the Central Universities,Beihang University&Capital Medical University Advanced Innovation Center for Big Data-Based Precision Medicine Plan(BHME-201804,BHME-201904) The Special Fund of the Pediatric Medical Coordinated Development Center of Beijing Hospitals 

主　　题：psychiatric disorders multitrait analysis of genome-wide association analysis novel loci Mendelian randomization causal effects 

摘      要：Different psychiatric disorders share genetic relationships and pleiotropic loci to certain *** integrated and analyzed datasets related to major depressive disorder(MDD),bipolar disorder(BIP),and schizophrenia(SCZ)from the Psychiatric Genomics Consortium using multitrait analysis of genome-wide association analysis(MTAG).MTAG significantly increased the effective sample size from 99,773 to 119,754 for MDD,from 909,061 to 1,450,972 for BIP,and from 856,677 to 940,613 for *** discovered 7,32,and 43 novel lead single nucleotide polymorphisms(SNPs)and 1,6,and 3 novel causal SNPs for MDD,BIP,and SCZ,respectively,after *** identified rs8039305 in the FURIN gene as a novel pleiotropic locus across the three *** performed marker analysis of genomic annotation(MAGMA)and Hi-C-coupled MAGMA(H-MAGMA)based gene-set analysis and identified 101 genes associated with the three disorders,which were enriched in the regulation of postsynaptic membranes,postsynaptic membrane dopaminergic synapses,and Notch signaling ***,we performed Mendelian randomization analysis using different tools and detected a causal effect of BIP on ***,we demonstrated the usage of combined genome-wide association studies summary statistics for exploring potential novel mechanisms of the three psychiatric disorders,providing an alternative approach to integrate publicly available summary data.