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| 利用条件错误发现率方法识别抑郁症和失眠症的多效性位点 |
| Identification of Genetic Loci That Overlap between Major Depressive Disorders and Insomnia Disorders using the Conditional False Discovery Rate Method |
| 投稿时间：2023-11-13 修订日期：2024-05-23 |
| DOI： |
| 中文关键词: 抑郁症 失眠症 基因多效性 条件性错误发现率 全基因组关联研究 |
| 英文关键词:Major dpressive disorders Insomnia disorders Pleiotropy Conditional false discovery rate Genome-wide association studies |
| 基金项目:深部经颅磁刺激对双相抑郁患者认知功能的影响及其机制 |
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| 中文摘要: |
| 背景 抑郁症和失眠症常共病存在，两者存在一些共同的发病机制，并可能受相同的多效性基因的调控，既往全基因组关联分析（GWAS）一般采用单性状研究，在解释基因多效性方面存在一定的狭窄性。目的 利用条件错误发现率（cFDR）方法对最近的GWAS数据进行分析，检验抑郁症和失眠症是否存在共同的遗传风险因素。方法 抑郁症GWAS数据来自精神疾病遗传学联盟（PGC），共包含246 363例抑郁症患者和561 190例正常对照。失眠症全基因组关联数据来自睡眠障碍知识门户，共包含1 331 010例受试者。采用cFDR和联合的条件错误发现率（ccFDR）方法筛选更多与抑郁症和失眠症相关的遗传位点，采用通路富集分析检验这些位点的生物学功能。结果 抑郁症和失眠症存在显著多效性富集现象。利用cFDR方法，以cFDR<0.01作为显著性阈值，鉴定出21个易感位点与抑郁症相关，其中17个是新识别的，38个易感位点与失眠症相关，有28个是新识别的。以ccFDR<0.05为显著性阈值，识别出16个多效性位点与抑郁症和失眠症均相关，其中15个是本研究新识别的。通路富集分析结果显示，这些易感位点富集于突触传递相关通路，如：突触后密度（GO:0014069，P=4.91E-04，FDR=4.84E-03），不对称突触（GO:0032279，P=5.09E-0，FDR=4.84E-03），突触后膜神经递质受体水平的调节（GO:0099072，P=5.11E-04，FDR=1.69E-02）。结论 失眠症与抑郁症之间存在多效性富集现象，其共病机制与突触传递有关。 |
| 英文摘要: |
| Background Major depressive disorders and insomnia disorders are often coexit, which have some common pathogenesis and may be regulated by the same pleiotropic genes. Previous GWAS studies generally used single-trait studies, which have certain limitations in explaining gene pleiotropic effects. Objective we aimed to examine whether major depressive disorders and insomnia disorders share genetic risk factors utilizing recent large-scale genome-wide association studies (GWAS). Methods The genome-wide association study （GWAS） data sets were downloaded from the Psychiatric Genomics Consortium(PGC) and Sleep Disorder Knowledge Portal. The major depressive disorders related GWAS data including 561 190 controls and 246 363 cases, and the insomnia disorders related GWAS data involving 1 331 010 subjects. the cFDR and ccFDR were used to identify pleiotropic genetic loci significantly associated with major depressive disorders and insomnia disorders. we used path enrichment analysis to further determine the biological functions of the susceptibility sites. Results There was significant genetic pleiotropic enrichment between major depressive disorders and insomnia disorders. Leveraging this enrichment, A total of 21 susceptibility loci and major depressive disorders were identified in this study with a significance threshold of cFDR<0.01, including 17 new genetic variation loci. At the same time, 38 genetic variation loci were identified with significant associations with insomnia disorders, including 28 newly discovered susceptibility loci. The ccFDR analysis identified 16 independent pleiotropic SNPs for both major depressive disorders and insomnia disorders(ccFDR<0.05), 15 of which were newly discovered. Pathway enrichment analysis showed that the enrichment of susceptibility loci associated with synaptic transmission, Such as postsynaptic density (GO:0014069; P=4.91E-04; FDR=4.84E-03), asymmetric synapse(GO:0032279; P=5.09E-04; FDR=4.84E-03), regulation of postsynaptic membrane neurotransmitter receptor levels(GO:0099072; P=5.11E-04; FDR=1.69E-02) .Conclusion Our study found that there was a significant pleiotropic enrichment between major depressive disorders and insomnia disorders, and the comorbidity mechanism was related to synaptic transmission. |
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