孟德尔随机化分析并没有揭示慢性疼痛的遗传倾向与自闭症谱系障碍之间的因果关系

IF 3.3 2区医学 Q2 PSYCHIATRY

Journal of Psychosomatic Research Pub Date : 2025-06-16 DOI:10.1016/j.jpsychores.2025.112189

Zheng Chen , Qiaoyun Yang , Shuibing Zhang , Dae-jung Yang , Tuochao Peng

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引用次数: 0

摘要

虽然观察性研究表明慢性疼痛（CP）和自闭症谱系障碍（ASD）之间存在潜在的合并症，但因果关系尚不清楚。本研究旨在通过双向孟德尔随机化（MR）分析，探讨CP和ASD遗传易感性之间的因果关系。方法CP和ASD的全基因组关联汇总数据来源于公共数据库。单核苷酸多态性（SNPs）作为MR分析的工具变量（IVs）。逆方差加权（IVW）是主要的MR方法，MR- egger、加权中位数和最大似然分析补充了IVW结果。正向MR分析评估CP对ASD的因果关系，反向MR分析评估ASD对CP的因果关系，并对MR结果的可靠性进行各种敏感性试验。结果前瞻性磁共振分析发现7种CP类型与ASD无因果关系(P >；0.05)。同样，反向MR分析显示ASD对7种CP类型没有因果关系(P >；0.05)。敏感性测试证实了结果的可靠性：(i)科克伦Q检验显示不存在显著的异质性；（ii） MR-Egger截距检验和MR-PRESSO全局检验均未发现水平多效性；（iii）留一试验证实了MR结果的稳定性。结论双向MR分析未发现CP遗传倾向与ASD之间存在因果关系的证据。观察到的共病可能是由于共同的机制，而不是直接的因果关系。需要进一步的研究来探索这些机制并为治疗策略提供信息。

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Mendelian randomization analysis does not reveal a causal association between genetic liability to chronic pain and autism spectrum disorder

Objective

Although observational studies suggest potential comorbidities between chronic pain (CP) and autism spectrum disorder (ASD), causal relationship remains unclear. This study aimed to investigate the causal association between genetic liability to CP and ASD using a bidirectional Mendelian Randomization (MR) analysis.

Methods

Genome-wide association summary-level data for CP and ASD were sourced from public databases. Single nucleotide polymorphisms (SNPs) were used as instrumental variables (IVs) in MR analysis. Inverse variance weighted (IVW) was the primary MR method, with MR-Egger, weighted median, and maximum likelihood analyses supplementing IVW results. Forward MR analysis evaluated the causal effect of CP on ASD, and reverse MR analysis assessed the causal impact of ASD on CP. Various sensitivity tests were performed for MR results' reliability.

Results

The forward MR analysis found no causal effect of seven CP types on ASD (P > 0.05). Similarly, reverse MR analysis showed no causal effect of ASD on seven CP types (P > 0.05). Sensitivity tests confirmed results' reliability: (i) Cochran's Q test showed no significant heterogeneity; (ii) MR-Egger intercept test and MR-PRESSO global test indicated no horizontal pleiotropy; (iii) leave-one-out test confirmed the stability of the MR results.

Conclusion

This bidirectional MR analysis did not find evidence for a causal relationship between genetic liability to CP and ASD. The observed comorbidity may be due to shared mechanisms rather than direct causation. Further research is needed to explore these mechanisms and inform therapeutic strategies.

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来源期刊

Journal of Psychosomatic Research 医学-精神病学

CiteScore

7.40

自引率

6.40%

发文量

314

审稿时长

6.2 weeks

期刊介绍： The Journal of Psychosomatic Research is a multidisciplinary research journal covering all aspects of the relationships between psychology and medicine. The scope is broad and ranges from basic human biological and psychological research to evaluations of treatment and services. Papers will normally be concerned with illness or patients rather than studies of healthy populations. Studies concerning special populations, such as the elderly and children and adolescents, are welcome. In addition to peer-reviewed original papers, the journal publishes editorials, reviews, and other papers related to the journal''s aims.