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Brain transcriptome-wide association study implicates novel risk genes underlying schizophrenia risk

Published online by Cambridge University Press:  24 April 2023

Chengcheng Zhang ,
Xiaojing Li ,
Liansheng Zhao ,
Wanjun Guo ,
Wei Deng ,
Qiang Wang ,
Xun Hu ,
Xiangdong Du ,
Pak Chung Sham  and
Xiongjian Luo
...Show all authors
Chengcheng Zhang
Affiliation:
Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China
Xiaojing Li
Affiliation:
Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China
Liansheng Zhao
Affiliation:
Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China
Wanjun Guo
Affiliation:
Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China
Wei Deng
Affiliation:
Affiliated Mental Health Center & Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
Qiang Wang
Affiliation:
Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China
Xun Hu
Affiliation:
The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
Xiangdong Du
Affiliation:
Suzhou Psychiatric Hospital, Soochow University's Affiliated Guangji Hospital, Suzhou, Jiangsu, China
Pak Chung Sham
Affiliation:
Department of Psychiatry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China Centre for PanorOmic Sciences, The University of Hong Kong, Hong Kong SAR, China State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR, China
Xiongjian Luo
Affiliation:
Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China
Tao Li*
Affiliation:
Affiliated Mental Health Center & Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangzhou, China
*
Corresponding author: Tao Li, E-mail: litaozjusc@zju.edu.cn
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Abstract

Background

To identify risk genes whose expression are regulated by the reported risk variants and to explore the potential regulatory mechanism in schizophrenia (SCZ).

Methods

We systematically integrated three independent brain expression quantitative traits (eQTLs) (CommonMind, GTEx, and BrainSeq Phase 2, a total of 1039 individuals) and GWAS data (56 418 cases and 78 818 controls), with the use of transcriptome-wide association study (TWAS). Diffusion magnetic resonance imaging was utilized to quantify the integrity of white matter bundles and determine whether polygenic risk of novel genes linked to brain structure was present in patients with first-episode antipsychotic SCZ.

Results

TWAS showed that eight risk genes (CORO7, DDAH2, DDHD2, ELAC2, GLT8D1, PCDHA8, THOC7, and TYW5) reached transcriptome-wide significance (TWS) level. These findings were confirmed by an independent integrative approach (i.e. Sherlock). We further conducted conditional analyses and identified the potential risk genes that driven the TWAS association signal in each locus. Gene expression analysis showed that several TWS genes (including CORO7, DDAH2, DDHD2, ELAC2, GLT8D1, THOC7 and TYW5) were dysregulated in the dorsolateral prefrontal cortex of SCZ cases compared with controls. TWS genes were mainly expressed on the surface of glutamatergic neurons, GABAergic neurons, and microglia. Finally, SCZ cases had a substantially greater TWS genes-based polygenic risk (PRS) compared to controls, and we showed that fractional anisotropy of the cingulum-hippocampus mediates the influence of TWS genes PRS on SCZ.

Conclusions

Our findings identified novel SCZ risk genes and highlighted the importance of the TWS genes in frontal-limbic dysfunctions in SCZ, indicating possible therapeutic targets.

Keywords

eQTLGWASschizophreniaTWASwhite matter tract
Type
Original Article
Information
Psychological Medicine , Volume 53 , Issue 14 , October 2023 , pp. 6867 - 6877
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Copyright
Copyright © The Author(s), 2023. Published by Cambridge University Press

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References

Aguet, F., Brown, A. A., Castel, S. E., Davis, J. R., He, Y., Jo, B., … Biospecimen Collection Source Site, N. (2017). Genetic effects on gene expression across human tissues. Nature, 550(7675), 204–213. doi:10.1038/nature24277.Google Scholar
Brzezniak, L. K., Bijata, M., Szczesny, R. J., & Stepien, P. P. (2011). Involvement of human ELAC2 gene product in 3′ end processing of mitochondrial tRNAs. RNA Biology, 8(4), 616–626. doi:10.4161/rna.8.4.15393.CrossRefGoogle ScholarPubMed
Charlson, F. J., Ferrari, A. J., Santomauro, D. F., Diminic, S., Stockings, E., Scott, J. G., … Whiteford, H. A. (2018). Global epidemiology and burden of schizophrenia: Findings from the global burden of disease study 2016. Schizophrenia Bulletin, 44(6), 1195–1203. doi:10.1093/schbul/sby058.CrossRefGoogle ScholarPubMed
Chen, Q., Ursini, G., Romer, A. L., Knodt, A. R., Mezeivtch, K., Xiao, E., … Weinberger, D. R. (2018). Schizophrenia polygenic risk score predicts mnemonic hippocampal activity. Brain, 141(4), 1218–1228. doi:10.1093/brain/awy004.CrossRefGoogle ScholarPubMed
Collado-Torres, L., Burke, E. E., Peterson, A., Shin, J., Straub, R. E., Rajpurohit, A., … Jaffe, A. E. (2019). Regional heterogeneity in gene expression, regulation, and coherence in the frontal Cortex and hippocampus across development and schizophrenia. Neuron, 103(2), 203–216.e208. doi:10.1016/j.neuron.2019.05.013.CrossRefGoogle ScholarPubMed
Cosgrove, D., Mothersill, O., Kendall, K., Konte, B., Harold, D., Giegling, I., … The Wellcome Trust Case Control, C. (2017). Cognitive characterization of schizophrenia risk variants involved in synaptic transmission: Evidence of CACNA1C's role in working memory. Neuropsychopharmacology, 42(13), 2612–2622. doi:10.1038/npp.2017.123.CrossRefGoogle ScholarPubMed
Crossley, N. A., Mechelli, A., Scott, J., Carletti, F., Fox, P. T., McGuire, P., & Bullmore, E. T. (2014). The hubs of the human connectome are generally implicated in the anatomy of brain disorders. Brain, 137(Pt 8), 2382–2395. doi:10.1093/brain/awu132.CrossRefGoogle ScholarPubMed
Davies, G., Lam, M., Harris, S. E., Trampush, J. W., Luciano, M., Hill, W. D., … Deary, I. J. (2018). Study of 300486 individuals identifies 148 independent genetic loci influencing general cognitive function. Nature Communications, 9(1), 2098. doi:10.1038/s41467-018-04362-x.CrossRefGoogle Scholar
Dong, Z., Ma, Y., Zhou, H., Shi, L., Ye, G., Yang, L., … Zhou, L. (2020). Integrated genomics analysis highlights important SNPs and genes implicated in moderate-to-severe asthma based on GWAS and eQTL datasets. BMC Pulmonary Medicine, 20(1), 270. doi:10.1186/s12890-020-01303-7.CrossRefGoogle ScholarPubMed
Ferrarelli, F., Sarasso, S., Guller, Y., Riedner, B. A., Peterson, M. J., Bellesi, M., … Tononi, G. (2012). Reduced natural oscillatory frequency of frontal thalamocortical circuits in schizophrenia. Archives of General Psychiatry, 69(8), 766–774. doi:10.1001/archgenpsychiatry.2012.147.CrossRefGoogle ScholarPubMed
Fettes, P., Schulze, L., & Downar, J. (2017). Cortico-striatal-thalamic loop circuits of the orbitofrontal Cortex: Promising therapeutic targets in psychiatric illness. Frontiers in Systems Neuroscience, 11, 25. doi:10.3389/fnsys.2017.00025.CrossRefGoogle ScholarPubMed
Fornito, A., Yücel, M., Dean, B., Wood, S. J., & Pantelis, C. (2009). Anatomical abnormalities of the anterior cingulate cortex in schizophrenia: Bridging the gap between neuroimaging and neuropathology. Schizophrenia Bulletin, 35(5), 973–993. doi:10.1093/schbul/sbn025.CrossRefGoogle ScholarPubMed
Fromer, M., Roussos, P., Sieberts, S. K., Johnson, J. S., Kavanagh, D. H., Perumal, T. M., … Sklar, P. (2016). Gene expression elucidates functional impact of polygenic risk for schizophrenia. Nature Neuroscience, 19(11), 1442–1453. doi:10.1038/nn.4399.CrossRefGoogle ScholarPubMed
Goes, F. S., McGrath, J., Avramopoulos, D., Wolyniec, P., Pirooznia, M., Ruczinski, I., … Pulver, A. E. (2015). Genome-wide association study of schizophrenia in Ashkenazi Jews. American Journal of Medical Genetics Part B, 168(8), 649–659. doi:10.1002/ajmg.b.32349.CrossRefGoogle ScholarPubMed
Gusev, A., Ko, A., Shi, H., Bhatia, G., Chung, W., Penninx, B. W. J. H., … Pasaniuc, B. (2016). Integrative approaches for large-scale transcriptome-wide association studies. Nature Genetics, 48(3), 245–252. doi:10.1038/ng.3506.CrossRefGoogle ScholarPubMed
Hagenaars, S. P., Harris, S. E., Davies, G., Hill, W. D., Liewald, D. C. M., Ritchie, S. J., … Longevity, G. (2016). Shared genetic aetiology between cognitive functions and physical and mental health in UK Biobank (N=112 151) and 24 GWAS consortia. Molecular Psychiatry, 21(11), 1624–1632. doi:10.1038/mp.2015.225.CrossRefGoogle ScholarPubMed
Harrison, P. J. (2015). Recent genetic findings in schizophrenia and their therapeutic relevance. Journal of Psychopharmacology (Oxford, England), 29(2), 85–96. doi:10.1177/0269881114553647.CrossRefGoogle ScholarPubMed
Hayes, A. F., & Preacher, K. J. (2014). Statistical mediation analysis with a multicategorical independent variable. The British Journal of Mathematical and Statistical Psychology, 67(3), 451–470. doi:10.1111/bmsp.12028.CrossRefGoogle ScholarPubMed
He, X., Fuller, C. K., Song, Y., Meng, Q., Zhang, B., Yang, X., & Li, H. (2013). Sherlock: Detecting gene-disease associations by matching patterns of expression QTL and GWAS. The American Journal of Human Genetics, 92(5), 667–680.CrossRefGoogle ScholarPubMed
Heath, C. G., Viphakone, N., & Wilson, S. A. (2016). The role of TREX in gene expression and disease. Biochemical Journal, 473(19), 2911–2935. doi:10.1042/bcj20160010.CrossRefGoogle ScholarPubMed
Hibar, D. P., Stein, J. L., Renteria, M. E., Arias-Vasquez, A., Desrivières, S., Jahanshad, N., … Medland, S. E. (2015). Common genetic variants influence human subcortical brain structures. Nature, 520(7546), 224–229. doi:10.1038/nature14101.CrossRefGoogle ScholarPubMed
Hilker, R., Helenius, D., Fagerlund, B., Skytthe, A., Christensen, K., Werge, T. M., … Glenthøj, B. (2018). Heritability of schizophrenia and schizophrenia spectrum based on the nationwide Danish Twin Register. Biological Psychiatry, 83(6), 492–498. doi:10.1016/j.biopsych.2017.08.017.CrossRefGoogle ScholarPubMed
Hua, K., Zhang, J., Wakana, S., Jiang, H., Li, X., Reich, D. S., … Mori, S. (2008). Tract probability maps in stereotaxic spaces: Analyses of white matter anatomy and tract-specific quantification. NeuroImage, 39(1), 336–347. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724595/pdf/nihms35198.pdf.CrossRefGoogle ScholarPubMed
Ikeda, M., Takahashi, A., Kamatani, Y., Momozawa, Y., Saito, T., Kondo, K., … Iwata, N. (2019). Genome-wide association study detected novel susceptibility genes for schizophrenia and shared trans-populations/diseases genetic effect. Schizophrenia Bulletin, 45(4), 824–834. doi:10.1093/schbul/sby140.CrossRefGoogle ScholarPubMed
Inloes, J. M., Hsu, K.-L., Dix, M. M., Viader, A., Masuda, K., Takei, T., … Cravatt, B. F. (2014). The hereditary spastic paraplegia-related enzyme DDHD2 is a principal brain triglyceride lipase. Proceedings of the National Academy of Sciences, 111(41), 14924–14929. doi:10.1073/pnas.1413706111.CrossRefGoogle ScholarPubMed
Jaffe, A. E., Straub, R. E., Shin, J. H., Tao, R., Gao, Y., Collado-Torres, L., … Weinberger, D. R. (2018). Developmental and genetic regulation of the human cortex transcriptome illuminate schizophrenia pathogenesis. Nature Neuroscience, 21(8), 1117–1125. doi:10.1038/s41593-018-0197-y.CrossRefGoogle ScholarPubMed
Kalin, N. H. (2019). Prefrontal cortical and limbic circuit alterations in psychopathology. American Journal of Psychiatry, 176(12), 971–973. doi:10.1176/appi.ajp.2019.19101036.CrossRefGoogle ScholarPubMed
Kang, H. J., Kawasawa, Y. I., Cheng, F., Zhu, Y., Xu, X., Li, M., … Sedmak, G. (2011). Spatio-temporal transcriptome of the human brain. Nature, 478(7370), 483–489.CrossRefGoogle ScholarPubMed
Karlsgodt, K. H., Jacobson, S. C., Seal, M., & Fusar-Poli, P. (2012). The relationship of developmental changes in white matter to the onset of psychosis. Current Pharmaceutical Design, 18(4), 422–433. doi:10.2174/138161212799316073.CrossRefGoogle Scholar
Katahira, J., Senokuchi, K., & Hieda, M. (2020). Human THO maintains the stability of repetitive DNA. Genes to Cells, 25(5), 334–342. https://doi.org/10.1111/gtc.12760.CrossRefGoogle ScholarPubMed
Kato, M., Araiso, Y., Noma, A., Nagao, A., Suzuki, T., Ishitani, R., & Nureki, O. (2011). Crystal structure of a novel JmjC-domain-containing protein, TYW5, involved in tRNA modification. Nucleic Acids Research, 39(4), 1576–1585.CrossRefGoogle ScholarPubMed
Korologou-Linden, R., Leyden, G. M., Relton, C. L., Richmond, R. C., & Richardson, T. G. (2021). Multi-omics analyses of cognitive traits and psychiatric disorders highlights brain-dependent mechanisms. Human Molecular Genetics, 32(6), 885–896. doi:10.1093/hmg/ddab016.CrossRefGoogle ScholarPubMed
Lam, M., Chen, C.-Y., Li, Z., Martin, A. R., Bryois, J., Ma, X., … Brown, B. C. (2019). Comparative genetic architectures of schizophrenia in East Asian and European populations. Nature Genetics, 51(12), 1670–1678.CrossRefGoogle ScholarPubMed
Maruyama, T., Baba, T., Maemoto, Y., Hara-Miyauchi, C., Hasegawa-Ogawa, M., Okano, H. J., … Tani, K. (2018). Loss of DDHD2, whose mutation causes spastic paraplegia, promotes reactive oxygen species generation and apoptosis. Cell Death and Disease, 9(8), 797. doi:10.1038/s41419-018-0815-3.CrossRefGoogle ScholarPubMed
McCutcheon, R. A., Abi-Dargham, A., & Howes, O. D. (2019). Schizophrenia, dopamine and the striatum: From biology to symptoms. Trends in Neurosciences, 42(3), 205–220. doi:10.1016/j.tins.2018.12.004.CrossRefGoogle ScholarPubMed
Nicolae, D. L., Gamazon, E., Zhang, W., Duan, S., Dolan, M. E., & Cox, N. J. (2010). Trait-associated SNPs are more likely to be eQTLs: Annotation to enhance discovery from GWAS. PLOS Genetics, 6(4), e1000888. doi:10.1371/journal.pgen.1000888.CrossRefGoogle ScholarPubMed
Ochoa, D., Hercules, A., Carmona, M., Suveges, D., Gonzalez-Uriarte, A., Malangone, C., … McDonagh, E. M. (2021). Open targets platform: Supporting systematic drug-target identification and prioritisation. Nucleic Acids Research, 49(D1), D1302–D1310. doi:10.1093/nar/gkaa1027.CrossRefGoogle ScholarPubMed
Pardiñas, A. F., Holmans, P., Pocklington, A. J., Escott-Price, V., Ripke, S., Carrera, N., … Walters, J. T. R. (2018). Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection. Nature Genetics, 50(3), 381–389. doi:10.1038/s41588-018-0059-2.CrossRefGoogle ScholarPubMed
Park, J., Jun, K., Choi, Y., Yoon, E., Kim, W., Jang, Y.-G., & Chung, J. (2021). CORO7 functions as a scaffold protein for the core kinase complex assembly of the Hippo pathway. Journal of Biological Chemistry, 296, 100040. doi:10.1074/jbc.RA120.013297.CrossRefGoogle ScholarPubMed
Periyasamy, S., John, S., Padmavati, R., Rajendren, P., Thirunavukkarasu, P., Gratten, J., … Mowry, B. J. (2019). Association of schizophrenia risk with disordered niacin metabolism in an Indian genome-wide association study. JAMA Psychiatry, 76(10), 1026–1034. doi:10.1001/jamapsychiatry.2019.1335.CrossRefGoogle Scholar
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A., Bender, D., … Sham, P. C. (2007). PLINK: A tool set for whole-genome association and population-based linkage analyses. The American Journal of Human Genetics, 81(3), 559–575. doi:10.1086/519795.CrossRefGoogle ScholarPubMed
Raju, V. B., Shukla, A., Jacob, A., Bharath, R. D., Kumar, V. K. G., Varambally, S., … Rao, N. P. (2021). The frontal pole and cognitive insight in schizophrenia. Psychiatry Research: Neuroimaging, 308, 111236. https://doi.org/10.1016/j.pscychresns.2020.111236.CrossRefGoogle ScholarPubMed
Ramos, J., & Fu, D. (2019). The emerging impact of tRNA modifications in the brain and nervous system. Biochimica et Biophysica Acta (BBA) – Gene Regulatory Mechanisms, 1862(3), 412–428. https://doi.org/10.1016/j.bbagrm.2018.11.007.CrossRefGoogle ScholarPubMed
Ripke, S., O'Dushlaine, C., Chambert, K., Moran, J. L., Kähler, A. K., Akterin, S., … Fromer, M. (2013). Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nature Genetics, 45(10), 1150.CrossRefGoogle ScholarPubMed
Rodriguez-López, J., Arrojo, M., Paz, E., Páramo, M., & Costas, J. (2020). Identification of relevant hub genes for early intervention at gene coexpression modules with altered predicted expression in schizophrenia. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 98, 109815.CrossRefGoogle ScholarPubMed
Savage, J. E., Jansen, P. R., Stringer, S., Watanabe, K., Bryois, J., de Leeuw, C. A., … Posthuma, D. (2018). Genome-wide association meta-analysis in 269867 individuals identifies new genetic and functional links to intelligence. Nature Genetics, 50(7), 912–919. doi:10.1038/s41588-018-0152-6.CrossRefGoogle Scholar
Schizophrenia Working Group of the Psychiatric Genomics, C. (2014). Biological insights from 108 schizophrenia-associated genetic loci. Nature, 511(7510), 421–427.CrossRefGoogle Scholar
Sigmundsson, T., Suckling, J., Maier, M., Williams, S., Bullmore, E., Greenwood, K., … Toone, B. (2001). Structural abnormalities in frontal, temporal, and limbic regions and interconnecting white matter tracts in schizophrenic patients with prominent negative symptoms. American Journal of Psychiatry, 158(2), 234–243. doi:10.1176/appi.ajp.158.2.234.CrossRefGoogle ScholarPubMed
Smeland, O. B., Frei, O., Kauppi, K., Hill, W. D., Li, W., Wang, Y., … Neuro, C. C. W. G. (2017). Identification of genetic loci jointly influencing schizophrenia risk and the cognitive traits of verbal-numerical reasoning, reaction time, and general cognitive function. JAMA Psychiatry, 74(10), 1065–1075. doi:10.1001/jamapsychiatry.2017.1986.CrossRefGoogle ScholarPubMed
Timshel, P. N., Thompson, J. J., & Pers, T. H. (2020). Genetic mapping of etiologic brain cell types for obesity. Elife, 9, e55851. doi:10.7554/eLife.55851.CrossRefGoogle ScholarPubMed
Wainberg, M., & Sinnott-Armstrong, N. (2019). Opportunities and challenges for transcriptome-wide association studies. 51(4), 592–599. doi:10.1038/s41588-019-0385-z.CrossRefGoogle Scholar
Wander, C. (2020). Schizophrenia: Opportunities to improve outcomes and reduce economic burden through managed care. The American Journal of Managed Care, 26(3 Suppl), S62–S68. doi:10.37765/ajmc.2020.43013.Google ScholarPubMed
Wang, J. Y., Li, X. Y., Li, H. J., Liu, J. W., Yao, Y. G., Li, M., … Luo, X. J. (2021). Integrative analyses followed by functional characterization reveal TMEM180 as a schizophrenia risk gene. Schizophrenia Bulletin, 47(5), 1364–1374. doi:10.1093/schbul/sbab032.CrossRefGoogle ScholarPubMed
Watanabe, K., Taskesen, E., Van Bochoven, A., & Posthuma, D. (2017). Functional mapping and annotation of genetic associations with FUMA. Nature Communications, 8(1), 1826.CrossRefGoogle ScholarPubMed
Wu, Q., & Maniatis, T. (1999). A striking organization of a large family of human neural cadherin-like cell adhesion genes. Cell, 97(6), 779–790. doi:10.1016/S0092-8674(00)80789-8.CrossRefGoogle ScholarPubMed
Wu, Q., Wang, X., Wang, Y., Long, Y. J., Zhao, J. P., & Wu, R. R. (2021). Developments in biological mechanisms and treatments for negative symptoms and cognitive dysfunction of schizophrenia. Neuroscience Bulletin, 37(11), 1609–1624. doi:10.1007/s12264-021-00740-6.CrossRefGoogle ScholarPubMed
Xiao, Y., Sun, H., Shi, S., Jiang, D., Tao, B., Zhao, Y., … Lui, S. (2018). White matter abnormalities in never-treated patients with long-term schizophrenia. American Journal of Psychiatry, 175(11), 1129–1136.CrossRefGoogle ScholarPubMed
Yang, C.-P., Li, X., Wu, Y., Shen, Q., Zeng, Y., Xiong, Q., … Luo, X.-J. (2018). Comprehensive integrative analyses identify GLT8D1 and CSNK2B as schizophrenia risk genes. Nature Communications, 9(1), 838. doi:10.1038/s41467-018-03247-3.CrossRefGoogle ScholarPubMed
Yeatman, J. D., Richie-Halford, A., Smith, J. K., Keshavan, A., & Rokem, A. (2018). A browser-based tool for visualization and analysis of diffusion MRI data. Nature Communications, 9(1), 940. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838108/pdf/41467_2018_Article_3297.pdf.CrossRefGoogle ScholarPubMed
Zhang, C., Ni, P., Liu, Y., Tian, Y., Wei, J., Xiang, B., … Li, T. (2020). GABAergic abnormalities associated with sensorimotor cortico-striatal community structural deficits in ErbB4 knockout mice and first-episode treatment-naïve patients with schizophrenia. Neuroscience Bulletin, 36(2), 97–109. doi:10.1007/s12264-019-00416-2.CrossRefGoogle ScholarPubMed
Zhang, Q., Nogales-Cadenas, R., Lin, J.-R., Zhang, W., Cai, Y., Vijg, J., & Zhang, Z. D. (2016). Systems-level analysis of human aging genes shed new light on mechanisms of aging. Human Molecular Genetics, 25(14), 2934–2947. doi:10.1093/hmg/ddw145.Google ScholarPubMed
Zhang, W., Olivi, A., Hertig, S. J., van Zijl, P., & Mori, S. (2008). Automated fiber tracking of human brain white matter using diffusion tensor imaging. Neuroimage, 42(2), 771–777. doi:10.1016/j.neuroimage.2008.04.241.CrossRefGoogle ScholarPubMed
Zhu, Z., Zhang, F., Hu, H., Bakshi, A., Robinson, M. R., Powell, J. E., … Yang, J. (2016). Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets. Nature Genetics, 48(5), 481–487. doi:10.1038/ng.3538.CrossRefGoogle ScholarPubMed
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