常见变异与精神分裂症风险相关：GWAS 数据的通路分析。
Common variants conferring risk of schizophrenia: a pathway analysis of GWAS data.
机构信息
Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
出版信息
Schizophr Res. 2010 Sep;122(1-3):38-42. doi: 10.1016/j.schres.2010.07.001. Epub 2010 Jul 24.
Abstract
Unlike the typical analysis of single markers in genome-wide association studies (GWAS), we incorporated Gene Set Enrichment Analysis (GSEA) and hypergeometric test and combined them using Fisher's combined method to perform pathway-based analysis in order to detect genes' combined effects on mediating schizophrenia. A few pathways were consistently found to be top ranked and likely associated with schizophrenia by these methods; they are related to metabolism of glutamate, the process of apoptosis, inflammation, and immune system (e.g., glutamate metabolism pathway, TGF-beta signaling pathway, and TNFR1 pathway). The genes involved in these pathways had not been detected by single marker analysis, suggesting this approach may complement the original analysis of GWAS dataset.
摘要
与全基因组关联研究（GWAS）中分析单个标记不同，我们采用了基因集富集分析（GSEA）和超几何检验，并使用 Fisher 合并方法将它们结合起来，以进行基于通路的分析，从而检测基因对介导精神分裂症的综合影响。通过这些方法，我们发现一些通路始终名列前茅，可能与精神分裂症有关；它们与谷氨酸代谢、细胞凋亡过程、炎症和免疫系统有关（例如，谷氨酸代谢途径、TGF-β信号通路和 TNFR1 途径）。参与这些通路的基因在单个标记分析中未被检测到，这表明该方法可能补充了 GWAS 数据集的原始分析。
相似文献
1
Common variants conferring risk of schizophrenia: a pathway analysis of GWAS data.
Schizophr Res. 2010 Sep;122(1-3):38-42. doi: 10.1016/j.schres.2010.07.001. Epub 2010 Jul 24.
2
Rare Pathogenic Variants in Genes Implicated in Glutamatergic Neurotransmission Pathway Segregate with Schizophrenia in Pakistani Families.
Genes (Basel). 2021 Nov 26;12(12):1899. doi: 10.3390/genes12121899.
3
A bias-reducing pathway enrichment analysis of genome-wide association data confirmed association of the MHC region with schizophrenia.
J Med Genet. 2012 Feb;49(2):96-103. doi: 10.1136/jmedgenet-2011-100397. Epub 2011 Dec 20.
4
Pathway analyses implicate glial cells in schizophrenia.
PLoS One. 2014 Feb 24;9(2):e89441. doi: 10.1371/journal.pone.0089441. eCollection 2014.
5
Protein-interaction-network-based analysis for genome-wide association analysis of schizophrenia in Han Chinese population.
J Psychiatr Res. 2014 Mar;50:73-8. doi: 10.1016/j.jpsychires.2013.11.014. Epub 2013 Dec 13.
6
Comprehensive pathway analyses of schizophrenia risk loci point to dysfunctional postsynaptic signaling.
Schizophr Res. 2018 Sep;199:195-202. doi: 10.1016/j.schres.2018.03.032. Epub 2018 Apr 11.
7
Hypothesis-driven candidate genes for schizophrenia compared to genome-wide association results.
Psychol Med. 2012 Mar;42(3):607-16. doi: 10.1017/S0033291711001607. Epub 2011 Aug 19.
8
Searching joint association signals in CATIE schizophrenia genome-wide association studies through a refined integrative network approach.
BMC Genomics. 2012;13 Suppl 6(Suppl 6):S15. doi: 10.1186/1471-2164-13-S6-S15. Epub 2012 Oct 26.
9
SNP-based pathway enrichment analysis for genome-wide association studies.
BMC Bioinformatics. 2011 Apr 15;12:99. doi: 10.1186/1471-2105-12-99.
10
Evidence for Association of Cell Adhesion Molecules Pathway and NLGN1 Polymorphisms with Schizophrenia in Chinese Han Population.
PLoS One. 2015 Dec 16;10(12):e0144719. doi: 10.1371/journal.pone.0144719. eCollection 2015.
引用本文的文献
1
Association of TNF and TLR2 genes with blood parameter levels in Mexican patients with schizophrenia.
BMC Psychiatry. 2025 Aug 22;25(1):806. doi: 10.1186/s12888-025-07270-9.
2
Structure-function coupling changes in first-episode, treatment-naïve schizophrenia correlate with cell type-specific transcriptional signature.
BMC Med. 2024 Oct 23;22(1):491. doi: 10.1186/s12916-024-03714-3.
3
Toll-Like Receptor () , and Gene Polymorphisms Support Evidence of Innate Immune Factors in Schizophrenia.
Neuropsychiatr Dis Treat. 2023 Nov 2;19:2353-2361. doi: 10.2147/NDT.S420952. eCollection 2023.
4
Statistical Bioinformatics to Uncover the Underlying Biological Mechanisms That Linked Smoking with Type 2 Diabetes Patients Using Transcritpomic and GWAS Analysis.
Molecules. 2022 Jul 8;27(14):4390. doi: 10.3390/molecules27144390.
5
Incorporating regulatory interactions into gene-set analyses for GWAS data: A controlled analysis with the MAGMA tool.
PLoS Comput Biol. 2022 Mar 22;18(3):e1009908. doi: 10.1371/journal.pcbi.1009908. eCollection 2022 Mar.
6
Relationship between TNF-α levels and psychiatric symptoms in first-episode drug-naïve patients with schizophrenia before and after risperidone treatment and in chronic patients.
BMC Psychiatry. 2021 Nov 11;21(1):561. doi: 10.1186/s12888-021-03569-5.
7
Systematic discovery of signaling pathways linking immune activation to schizophrenia.
iScience. 2021 Oct 2;24(11):103209. doi: 10.1016/j.isci.2021.103209. eCollection 2021 Nov 19.
8
Rewired Pathways and Disrupted Pathway Crosstalk in Schizophrenia Transcriptomes by Multiple Differential Coexpression Methods.
Genes (Basel). 2021 Apr 29;12(5):665. doi: 10.3390/genes12050665.
9
Cytokine Imbalance in Schizophrenia. From Research to Clinic: Potential Implications for Treatment.
Front Psychiatry. 2021 Mar 5;12:536257. doi: 10.3389/fpsyt.2021.536257. eCollection 2021.
10
Association of Candidate Single Nucleotide Polymorphisms Related to Candidate Genes in Patients With Schizophrenia.
Basic Clin Neurosci. 2020 Sep-Oct;11(5):595-608. doi: 10.32598/bcn.9.10.470. Epub 2020 Sep 1.
本文引用的文献
1
Schizophrenia gene networks and pathways and their applications for novel candidate gene selection.
PLoS One. 2010 Jun 29;5(6):e11351. doi: 10.1371/journal.pone.0011351.
2
Molecular pathways involved in neuronal cell adhesion and membrane scaffolding contribute to schizophrenia and bipolar disorder susceptibility.
Mol Psychiatry. 2011 Mar;16(3):286-92. doi: 10.1038/mp.2010.7. Epub 2010 Feb 16.
3
Comparing gene set analysis methods on single-nucleotide polymorphism data from Genetic Analysis Workshop 16.
BMC Proc. 2009 Dec 15;3 Suppl 7(Suppl 7):S96. doi: 10.1186/1753-6561-3-s7-s96.
4
A multi-dimensional evidence-based candidate gene prioritization approach for complex diseases-schizophrenia as a case.
Bioinformatics. 2009 Oct 1;25(19):2595-6602. doi: 10.1093/bioinformatics/btp428. Epub 2009 Jul 14.
5
Common polygenic variation contributes to risk of schizophrenia and bipolar disorder.
Nature. 2009 Aug 6;460(7256):748-52. doi: 10.1038/nature08185. Epub 2009 Jul 1.
6
Common variants on chromosome 6p22.1 are associated with schizophrenia.
Nature. 2009 Aug 6;460(7256):753-7. doi: 10.1038/nature08192. Epub 2009 Jul 1.
7
Common variants conferring risk of schizophrenia.
Nature. 2009 Aug 6;460(7256):744-7. doi: 10.1038/nature08186. Epub 2009 Jul 1.
8
Gene ontology analysis of GWA study data sets provides insights into the biology of bipolar disorder.
Am J Hum Genet. 2009 Jul;85(1):13-24. doi: 10.1016/j.ajhg.2009.05.011. Epub 2009 Jun 18.
9
Genetics of psychosis; insights from views across the genome.
Hum Genet. 2009 Jul;126(1):3-12. doi: 10.1007/s00439-009-0703-0. Epub 2009 Jun 12.
10
The dystrobrevin-binding protein 1 gene: features and networks.
Mol Psychiatry. 2009 Jan;14(1):18-29. doi: 10.1038/mp.2008.88. Epub 2008 Jul 29.
Zotero 插件