Phosphodiesterase and psychiatric disorders: a two-sample Mendelian randomization study.
Phosphodiesterase and psychiatric disorders: a two-sample Mendelian randomization study.
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DOI：
10.1186/s12967-023-04368-0
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发表时间：
2023-08-21
影响因子：
7.4
通讯作者：
Wang, Lifang
中科院分区：
文献类型：
--
作者：
Jiang, Miaomiao;Yan, Weiheng;Zhang, Yuyanan;Lu, Zhe;Lu, Tianlan;Zhang, Dai;Li, Jun;Wang, Lifang
在观察性研究中，磷酸二酯酶（PDEs）与精神疾病有关；然而，关联的因果关系仍未确定。具体来说，从全基因组关联研究（GWASs）中收集环核苷酸PDEs，包括通过水解环磷酸腺苷（cAMP）和环鸟苷单磷酸（cGMP） （PDE1A， PDE2A和PDE3A）获得的PDEs，特异性cGMP （PDE5A， PDE6D和PDE9A）和cAMP （PDE4D和PDE7A）。我们进行了双向双样本孟德尔随机化（MR）分析，以调查PDEs与九种精神疾病之间的关系。使用反方差加权法（IVW）、MR-Egger和加权中位数来估计因果效应。采用Cochran’s Q检验、MR- egger截距检验、MR Steiger检验、留一分析、漏斗图和MR多效残差和离群值（MR- presso）进行敏感性分析。cAMP特异性PDEs与高概率精神疾病相关。例如，PDE4D与精神分裂症（SCZ）（比值比(OR) = 1.0531, PIVW = 0.0414），以及重度抑郁症（MDD） （OR = 1.0329, PIVW = 0.0011）。同样，PDE7A与较高的注意力缺陷/多动障碍（ADHD）几率相关（OR = 1.0861, PIVW = 0.0038）。探索特定的PDE亚型和增加细胞内cAMP水平可以为有针对性的干预措施的发展提供信息。我们还观察到PDEs（能水解cAMP和cGMP）与精神疾病有关[自闭症谱系障碍中PDE1A的OR为1.0836；图雷特综合征（TS） PDE2A的OR值为0.8968，SCZ为0.9449；PDE3A诊断MDD的OR为0.9796；p < 0.05]。此外，精神障碍对PDEs也有一定的因果影响[强迫症对PDE6D升高，PDE2A和PDE4D降低；神经性厌食症对PDE9A降低的影响[j]。使用多重敏感性分析发现MR的结果是稳健的。在这项研究中，血浆PDE蛋白与精神疾病之间的潜在因果关系被确立。探索本研究未包括的其他PDE亚型可以更全面地了解PDE在精神疾病中的作用。开发针对PDE亚型的特异性药物可能是治疗精神疾病的一种有前途的治疗方法。在线版本包含补充材料，可在10.1186/s12967-023-04368-0获得。
Phosphodiesterases (PDEs) have been associated with psychiatric disorders in observational studies; however, the causality of associations remains unestablished. Specifically, cyclic nucleotide PDEs were collected from genome-wide association studies (GWASs), including PDEs obtained by hydrolyzing both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) (PDE1A, PDE2A, and PDE3A), specific to cGMP (PDE5A, PDE6D, and PDE9A) and cAMP (PDE4D and PDE7A). We performed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the relationship between PDEs and nine psychiatric disorders. The inverse-variance-weighted (IVW) method, MR-Egger, and weighted median were used to estimate causal effects. The Cochran’s Q test, MR-Egger intercept test, MR Steiger test, leave-one-out analyses, funnel plot, and MR pleiotropy residual sum and outlier (MR-PRESSO) were used for sensitivity analyses. The PDEs specific to cAMP were associated with higher-odds psychiatric disorders. For example, PDE4D and schizophrenia (SCZ) (odds ratios (OR) = 1.0531, PIVW = 0.0414), as well as major depressive disorder (MDD) (OR = 1.0329, PIVW = 0.0011). Similarly, PDE7A was associated with higher odds of attention-deficit/hyperactivity disorder (ADHD) (OR = 1.0861, PIVW = 0.0038). Exploring specific PDE subtypes and increase intracellular cAMP levels can inform the development of targeted interventions. We also observed PDEs (which hydrolyzes both cAMP and cGMP) was associated with psychiatric disorders [OR of PDE1A was 1.0836 for autism spectrum disorder; OR of PDE2A was 0.8968 for Tourette syndrome (TS) and 0.9449 for SCZ; and OR of PDE3A was 0.9796 for MDD; P < 0.05]. Furthermore, psychiatric disorders also had some causal effects on PDEs [obsessive–compulsive disorder on increased PDE6D and decreased PDE2A and PDE4D; anorexia nervosa on decreased PDE9A]. The results of MR were found to be robust using multiple sensitivity analysis. In this study, potential causal relationships between plasma PDE proteins and psychiatric disorders were established. Exploring other PDE subtypes not included in this study could provide a more comprehensive understanding of the role of PDEs in psychiatric disorders. The development of specific medications targeting PDE subtypes may be a promising therapeutic approach for treating psychiatric disorders. The online version contains supplementary material available at 10.1186/s12967-023-04368-0.
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影响因子：
11
作者：
International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and OCD Collaborative Genetics Association Studies (OCGAS)
通讯作者：
International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and OCD Collaborative Genetics Association Studies (OCGAS)
影响因子：
7.7
作者：
Burgess, Stephen;Thompson, Simon G.
通讯作者：
Thompson, Simon G.
CD33和阿尔茨海默氏病的外围水平：一项双向孟德尔随机研究。
影响因子：
6.8
作者：
Gu, Xiaojing;Dou, Meng;Cao, Bei;Jiang, Zheng;Chen, Yongping
通讯作者：
Chen, Yongping
前额皮质中磷酸二酯酶 4D 的敲低可减轻小鼠慢性不可预测的压力诱发的抑郁样行为和记忆缺陷。
影响因子：
4.6
作者：
Wang ZZ;Yang WX;Zhang Y;Zhao N;Zhang YZ;Liu YQ;Xu Y;Wilson SP;O'Donnell JM;Zhang HT;Li YF
通讯作者：
Li YF
DOI：
10.1176/appi.ajp.2017.16121402
发表时间：
2017-09-01
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Duncan L;Yilmaz Z;Gaspar H;Walters R;Goldstein J;Anttila V;Bulik-Sullivan B;Ripke S;Eating Disorders Working Group of the Psychiatric Genomics Consortium;Thornton L;Hinney A;Daly M;Sullivan PF;Zeggini E;Breen G;Bulik CM
通讯作者：
Bulik CM