Constipation and Psychiatric Disorders: A Bidirectional Mendelian Randomization Study.

IF 1.6 4区医学 Q4 BIOCHEMICAL RESEARCH METHODS

Combinatorial chemistry & high throughput screening Pub Date : 2025-05-14 DOI:10.2174/0113862073378253250428071105

Xu Yang, Jie Kang, Xuan Zhang, Nan Sui

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引用次数: 0

Abstract

Background: Observational studies have shown a link between constipation (CN) and psychiatric disorders, including Schizophrenia (SP), Bipolar disorder (BD), Schizoaffective disorder (SD), and Parkinson's disease (PD). However, it is still unknown whether CN affects the occurrence and development of psychiatric disorders or whether psychiatric disorders cause the occurrence and development of CN. Therefore, this study used Mendelian randomization (MR) analysis to evaluate the relationship between CN and psychiatric disorders.

Method: We used genome-wide association studies (GWAS) to assess the relationship between constipation (N = 411, 623) and four psychiatric disorders, including SP ( N = 77, 096), BD (N = 51, 710), SD ( N = 210, 962), PD (N = 482, 730 ), using bidirectional MR analysis. Inverse variance weighting (IVW), MR Egger (ME) and Weighted median (WM) were used as causal analysis methods. Cochran's Q test, funnel plot, MR Egger intercept test and Leave-one-out analysis were used to detect sensitivity. Confounding factors were analyzed and eliminated by LDtrait to avoid influencing the final MR Analysis result.

Results: The results of positive MR analysis indicated that there was no evidence of influence of constipation on SP ( OR 1.043, 95%CI 0.946 - 1.149, P value = 0.398), BD (OR 1.114, 95%CI 0.995 - 1.248, P value = 0.062), SD (OR 0.934, 95%CI 0.674 - 1.294, P value = 0.682) and PD (OR 1.118, 95%CI 0.918 - 1.361, P value = 0.269) under gene prediction. Reverse MR analysis suggested that SP (OR 1.030, 95% CI 1.001-1.060, P value = 0.042) had a causal relationship with constipation. BD (OR 0.993, 95% CI 0.962-1.025, P value = 0.664), SD (OR 1.021, 95% CI 0.984-1.059, P value = 0.265) and PD (OR 1.004, 95% CI 0.974-1.035, P value = 0.790) were not associated with CN.

Conclusion: There was a positive association between SP and CN. CN may have no exact causal relationship with BD, SD and PD, and the interaction mechanism between these diseases needs to be further explored.

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便秘和精神疾病：一项双向孟德尔随机研究。

背景：观察性研究表明便秘（CN）与精神疾病之间存在联系，包括精神分裂症（SP）、双相情感障碍（BD）、分裂情感障碍（SD）和帕金森病（PD）。然而，CN是否影响精神障碍的发生和发展，或者精神障碍是否导致CN的发生和发展，目前尚不清楚。因此，本研究采用孟德尔随机化（MR）分析来评估CN与精神疾病的关系。方法：采用全基因组关联研究（GWAS）评估便秘（N = 411、623）与4种精神疾病(SP （N = 77、096）、BD （N = 51、710）、SD （N = 210、962）、PD （N = 482、730）的关系，采用双向MR分析。因果分析方法采用方差逆加权（IVW）、MR Egger （ME）和加权中位数（WM）。采用Cochran’s Q检验、漏斗图、MR Egger截距检验和留一分析检测敏感性。通过LDtrait分析和消除混杂因素，避免影响最终的MR分析结果。结果：MR阳性分析结果显示，在基因预测下，便秘对SP （OR 1.043, 95%CI 0.946 ~ 1.149， P值= 0.398）、BD （OR 1.114, 95%CI 0.995 ~ 1.248， P值= 0.062）、SD （OR 0.934, 95%CI 0.674 ~ 1.294， P值= 0.682）和PD （OR 1.118, 95%CI 0.918 ~ 1.361， P值= 0.269）无影响。反向MR分析提示SP （OR 1.030, 95% CI 1.001 ~ 1.060， P值= 0.042）与便秘有因果关系。BD （OR 0.993, 95% CI 0.962 ~ 1.025， P值= 0.664）、SD （OR 1.021, 95% CI 0.984 ~ 1.059， P值= 0.265）和PD （OR 1.004, 95% CI 0.974 ~ 1.035， P值= 0.790）与CN无关。结论：SP与CN呈正相关。CN与BD、SD、PD可能没有确切的因果关系，三者之间的相互作用机制有待进一步探讨。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Combinatorial chemistry & high throughput screening 化学-生化研究方法

CiteScore

3.10

自引率

5.60%

发文量

327

审稿时长

7.5 months

期刊介绍： Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal: Target identification and validation Assay design, development, miniaturization and comparison High throughput/high content/in silico screening and associated technologies Label-free detection technologies and applications Stem cell technologies Biomarkers ADMET/PK/PD methodologies and screening Probe discovery and development, hit to lead optimization Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) Chemical library design and chemical diversity Chemo/bio-informatics, data mining Compound management Pharmacognosy Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products) Natural Product Analytical Studies Bipharmaceutical studies of Natural products Drug repurposing Data management and statistical analysis Laboratory automation, robotics, microfluidics, signal detection technologies Current & Future Institutional Research Profile Technology transfer, legal and licensing issues Patents.