机构：[1]Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute ofZoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China[2]Kunming College of Life Science, University of Chinese Academy of Sciences,Kunming, 650204, China云南省第一人民医院[3]Department of Psychiatry, The First Affiliated Hospital of Kunming Medical College, Kunming, Yunnan 650031, China昆明医科大学附属第一医院内科科室精神科[4]StateKey Laboratory of Membrane Biology, PKU-IDG/McGovern Institute for Brain Research, School of Life Sciences, Peking University, Beijing 100871, China[5]State Key Laboratory of Cognitive Neuroscience and Learning, and IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875,China[6]CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China[7]Center forExcellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming, Yunnna 650223, China
Recent genome-wide association studies (GWAS) have identified multiple risk loci that show strong associations with schizophrenia. However, pinpointing the potential causal genes at the reported loci remains a major challenge. Here we identify candidate causal genes for schizophrenia using an integrative genomic approach. Sherlock integrative analysis shows that ALMS1, GLT8D1, and CSNK2B are schizophrenia risk genes, which are validated using independent brain expression quantitative trait loci (eQTL) data and integrative analysis method (SMR). Consistently, gene expression analysis in schizophrenia cases and controls further supports the potential role of these three genes in the pathogenesis of schizophrenia. Finally, we show that GLT8D1 and CSNK2B knockdown promote the proliferation and inhibit the differentiation abilities of neural stem cells, and alter morphology and synaptic transmission of neurons. These convergent lines of evidence suggest that the ALMS1, CSNK2B, and GLT8D1 genes may be involved in pathophysiology of schizophrenia.
基金：
the National Key Research and Development
Program of China (Stem Cell and Translational Research) (2016YFA0100900) and
Strategic Priority Research Program of the Chinese Academy of Sciences (XDB13000000)
to X.-J.L. and Y.C. This study was also was supported by the National Basic Research
Program of China (2017YFA0105201), the National Nature Science Foundation of China
(31722029 to X.-J.L., U1502224 and 81772996 to Y.C., 81672764 to C.-P.Y., 31670842 to
C.Z., and 31571150 to C.C.), Yunnan Applied Basic Research Projects (2014FA038,
2016FA009, and 2014FB182), Yunnan province High-Level talents Introduced program
2013HA021, and the Beijing Municipal Science and Technology Commission
(Z161100002616021 and Z161100000216154). C.-P.Y. was also supported by the Chinese
Academy of Sciences Western Light Program, Youth Innovation Promotion Association,
CAS. X.-J.L. was supported by the 1000 Young Talents Program. Y.-G.Y. was supported
by the Strategic Priority Research Program (B) of CAS (XDB02020003) and the Bureau
of Frontier Sciences and Education of CAS (QYZDJ-SSW-SMC005).
第一作者机构：[1]Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute ofZoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Cui-Ping Yang,Xiaoyan Li,Yong Wu,et al.Comprehensive integrative analyses identify GLT8D1 and CSNK2B as schizophrenia risk genes[J].NATURE COMMUNICATIONS.2018,9:doi:10.1038/s41467-018-03247-3.
APA：
Cui-Ping Yang,Xiaoyan Li,Yong Wu,Qiushuo Shen,Yong Zeng...&Xiong-Jian Luo.(2018).Comprehensive integrative analyses identify GLT8D1 and CSNK2B as schizophrenia risk genes.NATURE COMMUNICATIONS,9,
MLA：
Cui-Ping Yang,et al."Comprehensive integrative analyses identify GLT8D1 and CSNK2B as schizophrenia risk genes".NATURE COMMUNICATIONS 9.(2018)
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