研究成果

实验室近年来在生物信息学领域进行了系统的探索和研究，通过开发分析工具-整合数据资源-应用于复杂疾病研究三个层面的工作，揭示复杂疾病的生物学机制与致病机理，寻找可以用于早期识别与干预的生物标志，并取得了一系列的进展。迄今为止，在Nature、Science、Nature Genetics、Nature Review Genetics、Biological Psychiatry、Molecular Psychiatry、Nucleic Acids Research等国际知名杂志发表论文近70篇，发表文章累计影响因子逾500分，累计引用近万次。

其中，实验室的重要研究成果包括：

• 同临床医院合作，开展了国际上首个注意缺陷多动障碍执行抑制功能的全基因组关联研究（Yang L *, Chang S *, ......Wang J #, Wang Y # & Lu L, 2017, Molecular Psychiatry），使用Stroop色字-干扰测验评估1702例病例的执行抑制功能，最终在7p22.3上发现了一个和Stroop测验的词干扰时间显著相关的新的易感位点: rs11514810，取得了突破性的成果。


• 同临床医院合作，开展了世界上首个针对原发性干燥综合征的全基因组关联研究（Li Y*, Zhang K *, Chen H *, …, Wang J #& Zhang F #. 2013, Nature Genetics），通过对1845例病例和3777例健康对照样本的分析，鉴别出新的原发性干燥综合征易感基因：GTF2IRD1和GTF2I，取得了突破性的成果。


• 开发了针对调控型变异的分析工具rSNPBase (Guo et al., 2014, Nucleic Acids Research)，对全基因组范围内的单核苷酸多态性位点（SNP）的调控属性进行了注释；并在此基础上进行了重要升级--rVarBase (Guo et al., 2015, Nucleic Acids Research)，将注释类型扩展到拷贝数变异（CNVs）以及新生突变，并且整合了新的调控元件，从基因调控的角度对致病位点的调控功能进行预测。


• 开发了一系列具有国际影响力的精神疾病遗传学数据库，涵盖了从单一疾病遗传学分析（注意缺陷多动障碍遗传学数据库-ADHDgene: Zhang et al., 2012, Nucleic Acids Research），单一疾病多学科交叉分析（重症抑郁症多学科关联数据库-MK4MDD: Guo et al., 2012, PloS ONE），到多种疾病交叉分析（双相情感障碍交叉遗传学数据库-BDgene: Chang et al., 2013, Biological Psychiatry）的系统性研究，为揭示精神疾患的遗传机制提供了重要的信息资源与分析工具。 >


• 开发了基于通路（pathway）的全基因组关联学习数据网络分析平台—i-GSEA4GWAS（Zhang et al., 2010, Nucleic Acids Research） ，用于研究SNP的组合效应，鉴别与疾病表型相关的通路/基因集,并在此基础上通过改进算法和整合ENCODE、Ensembl和eQTLs数据得到新版本i-GSEA4GWAS v2.0（Zhang et al., 2015, Protein & Cell）；开发了探索致病变异的全基因组关联学习数据网络分析平台ICSNPathway（Zhang et al., 2011, Nucleic Acids Research>），以进一步研究和揭示疾病致病机理。


• 建立了基于网络的遗传学数据分析框架，挖掘与疾病相关的网络模块与生物学功能，并已经成功应用于精神分裂症 (Chang et al., 2015, PLoS One)和原发性干燥综合征 (Fang et al., 2015, Scientific Reports)。


• 通过生物信息学网络分析手段，比较了阿尔茨海默症，重症抑郁症、双相情感障碍等七类应激相关疾病致病基因间的关联(Guo et al., 2015, Scientific Reports)，并从差异表达基因的角度衡量了慢性应激这一环境因素对这些疾病的影响。


• 通过全基因组关联研究揭示了自身免疫疾病与精神/神经障碍共享的基因。通过将全基因组关联研究数据和候选基因关联研究数据整合分析，首次证明IL10基因上的多态性位点和单倍型与精神分裂症的易感性相关，为揭示精神分裂症的神经免疫学机制提供了遗传学证据（Gao et al., PLoS One, 2014）。

发表文章

1. Qu, S., Du, Y., Chang, S., Guo, L., Fang K., Li, Y., Zhang, F., Zhang, K. & Wang, J. (2017) Common variants near IKZF1 are associated with primary Sj?gren's syndrome in Han Chinese. PLoS One (in press)


2. Yang, L., Chang, S., Lu, Q., Zhang, Y., Wu, Z., Sun, X., Cao, Q., Qian, Y., Jia, T., Xu, B., Duan, Q., Li, Y., Zhang, K., Gunter, S., Lu, L., Liu, D., # Wang, J., # and Wang, Y.# Lu, L. (2017). A new locus regulating MICALL2 expression was identified for association with executive inhibition in children with attention deficit hyperactivity disorder. Mol Psychiatry. doi:10.1038/mp.2017.74


3. Wang, J., Qu, S., Wang, W., Guo, L., Zhang, K., Chang, S., & Wang, J.# (2016). A combined analysis of genome-wide expression profiling of bipolar disorder in human prefrontal cortex. J Psychiatr Res, 82, 23-29. doi: 10.1016/j.jpsychires.2016.07.016


4. Fang, K., Zhang, K., & Wang, J. (2015). Network-assisted analysis of primary Sjogren's syndrome GWAS data in Han Chinese. Sci Rep, 5, 18855. doi: 10.1038/srep18855


5. Guo, L., Du, Y., Qu, S., & Wang, J. (2015). rVarBase: an updated database for regulatory features of human variants. Nucleic Acids Res. doi: 10.1093/nar/gkv1107


6. Chang, S., Wang, J., Zhang, K., & Wang, J. (2015). Pathway-based analysis for genome-wide association study data of bipolar disorder provides new insights for genetic study. Protein Cell. doi: 10.1007/s13238-015-0201-1


7. Chang, S., Fang, K., Zhang, K., & Wang, J. (2015). Network-Based Analysis of Schizophrenia Genome-Wide Association Data to Detect the Joint Functional Association Signals. PLoS One, 10(7), e0133404. doi: 10.1371/journal.pone.0133404


8. Guo, L. Y., Du, Y., & Wang, J. (2015). Network analysis reveals a stress-affected common gene module among seven stress-related diseases/systems which provides potential targets for mechanism research. Scientific Reports, 5. doi: Artn 12939 10.1038/Srep12939 [Q1, IF: 5.578, 5-year IF: 5.597]


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12. Guo, L.Y., Du, Y.,Chang, S.H., Zhang, W.N., Wang, J. (2014). Applying differentially expressed genes from rodent models of chronic stress to researches of stress-related disease: an online database. Psychosomatic Medicine.


13. Li, Z.*, Chang, S., Zhang, L., Gao, L., & Wang, J. (2014). Molecular genetic studies of ADHD and its candidate genes: a review.Psychiatry Research, doi: 10.1016/j.psychres.2014.05.005


14. Gao, L., Li, Z., Chang, S., & Wang, J. (2014). Association of interleukin-10 polymorphisms with schizophrenia: a meta-analysis. PLoS One, 9(3), e90407. doi: 10.1371/journal.pone.0090407


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