| 宋文超,楚利君,马静.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[J].四川精神卫生杂志,2024,37(3):198-204.Song Wenchao,Chu Lijun,Ma Jing,Identification of genetic loci that overlap between major depressive disorder and insomnia using the conditional false discovery rate analysis[J].SICHUAN MENTAL HEALTH,2024,37(3):198-204 |
| 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 disorder and insomnia using the conditional false discovery rate analysis |
| 投稿时间：2023-11-13 |
| DOI：10.11886/scjsws20231113004 |
| 中文关键词: 抑郁症 失眠症 基因多效性 条件错误发现率 全基因组关联研究 |
| 英文关键词:Major depressive disorder Insomnia Pleiotropy Conditional false discovery rate Genome-wide association study |
| 基金项目:天津市卫生健康科技项目（项目名称：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，项目编号：TJWJ2021QN065）；天津市医学重点学科（专科）建设项目（项目编号：TJYXZDXK-033A） |
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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调控。既往全基因组关联研究（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 识别与失眠症和抑郁症相关的遗传变异位点，检验抑郁症和失眠症是否存在共同的遗传因素。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GWAS数据来自睡眠障碍知识门户，共包含1 331 010例受试者。采用条件错误发现率（cFDR）和联合的条件错误发现率（ccFDR）方法筛选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的多效性富集现象。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（其中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，与抑郁症和失眠症均关联的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 disorder and insomnia often coexist， and the two may share a mechanism of pathogenesis and be affected by common underlying genes with strong pleiotropic effects. Previous genome-wide association studies （GWAS） mainly focused on single-gene morphological characters analysis， which impose limitations on showing possible pleiotropic effects.Objective To identify genetic loci related to insomnia and major depressive disorder， and to examine whether there are common genetic factors underlying both insomnia and depression.Methods The GWAS data for major depressive disorder originates from the Psychiatric Genomics Consortium （PGC）， which comprises a total of 246 363 depressive cases and 561 190 controls. The insomnia GWAS data was downloaded from Sleep Disorder Knowledge Portal， involving 1 331 010 participants. Then the conditional false discovery rate （cFDR） and conjunction cFDR （ccFDR） were utilized to identify the genetic loci associated with major depressive disorder and insomnia， and pathway enrichment analysis was performed to examine the biological functions of these loci.Results A significant pleiotropic effect was detected between major depressive disorder and insomnia. By leveraging pleiotropic enrichment， 21 susceptibility loci （17 novel loci） for major depressive disorder and 38 susceptibility loci （28 novel loci） for insomnia were identified with the threshold of cFDR<0.01. A total of 16 pleiotropic loci （15 novel loci） related to both major depressive disorder and insomnia were identified with the threshold of ccFDR<0.05. pathway enrichment analysis indicated that the susceptibility loci were mainly enriched in synaptic transmission pathway， 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）， and regulation of postsynaptic membrane neurotransmitter receptor levels （GO：0099072， P=5.11E-04， FDR=1.69E-02）.Conclusion A significant pleiotropic enrichment is found between major depressive disorder and insomnia， and the comorbidity mechanism is related to synaptic transmission. ［Funded by Tianjin Health Science and Technology Project （number， TJWJ2021QN065）； Tianjin Key Medical Discipline （Specialty） Construction Project （number， TJYXZDXK-033A）］ |
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