Association between human herpesviruses infections and childhood neurodevelopmental disorders: insights from two-sample mendelian randomization analyses and systematic review with meta-analysis.

IF 3.2 3区医学 Q1 PEDIATRICS Italian Journal of Pediatrics Pub Date : 2024-11-20 DOI:10.1186/s13052-024-01820-9

Liwei Fang, Zuojun Wang, Jingyi Zhao, Xun Wu, Shunxin Wang, Hui Gao, De Wu

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Abstract

Background: The potential roles of viral infections in neurodevelopmental disorders (NDDs) have been suggested based on previous studies. Given the high prevalence of human herpesviruses (HHVs), the associations between HHVs infection and the risk of NDDs warrant explored.

Methods: Our study employs a two-sample Mendelian randomization (MR) analysis and systematic review with meta-analysis to investigate whether genetically predicted HHVs infection are linked to three main childhood NDDs-autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), and Tourette syndrome (TS). We utilized genetic variants associated with HHV infections in genome-wide association study (GWAS) summary datasets of European populations to establish instrumental variables and statistics for three NDDs obtained from Psychiatric Genomics Consortium. MR analysis was performed using inverse-variance weighted, MR Egger, weighted median, simple median, weighted mode, and MR-PRESSO. In addition, publications associating HHVs infection with three NDDs were systematically searched using PubMed, Web of Science, and three Chinese databases for meta-analyses.

Results: The MR results found no evidence to support a link between genetically predicted HHVs infection and the risk of NDDs based on existing datasets. Twenty-seven observational studies on children with HHVs infection and NDDs were considered eligible. Meta-analysis showed that cytomegalovirus and HHV-6 infection were related with ASD, while Epstein-Barr virus and cytomegalovirus infection were associated with TD in Chinese population.

Conclusions: These results contribute to a comprehensive understanding of the possibilities underlying HHV infections in affecting childhood NDDs. Further research is necessary to include larger and more robust statistics of HHV infections and NDDs.

Trial registration: This systematic review was registered at PROSPERO as CRD42024554169. Retrospectively registered 26 July 2024.

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人类疱疹病毒感染与儿童神经发育障碍之间的关系：从双样本亡羊补牢随机分析和荟萃分析系统综述中获得的启示。

背景：根据以往的研究，病毒感染在神经发育障碍（NDDs）中的潜在作用已被提出。鉴于人类疱疹病毒（HHVs）的高流行率，有必要探讨 HHVs 感染与 NDDs 风险之间的关联：我们的研究采用了双样本孟德尔随机化（MR）分析和系统综述与荟萃分析，以调查遗传预测的 HHVs 感染是否与三种主要的儿童 NDDs（自闭症谱系障碍（ASD）、注意缺陷多动障碍（ADHD）和抽动秽语综合征（TS））有关。我们利用欧洲人群全基因组关联研究（GWAS）汇总数据集中与 HHV 感染相关的遗传变异，建立了工具变量，并统计了从精神病基因组学联盟（Psychiatric Genomics Consortium）获得的三种 NDDs 的数据。使用反方差加权、MR Egger、加权中位数、简单中位数、加权模式和 MR-PRESSO 进行了 MR 分析。此外，还使用PubMed、Web of Science和三个中文数据库系统地检索了将HHVs感染与三种NDDs相关联的出版物，以进行荟萃分析：磁共振结果发现，根据现有数据集，没有证据支持基因预测的 HHVs 感染与 NDDs 风险之间存在联系。27项关于儿童 HHVs 感染和 NDDs 的观察性研究被认为符合条件。Meta分析表明，在中国人群中，巨细胞病毒和HHV-6感染与ASD相关，而Epstein-Barr病毒和巨细胞病毒感染与TD相关：这些结果有助于全面了解 HHV 感染影响儿童 NDD 的可能性。有必要开展进一步研究，以纳入更大规模、更可靠的 HHV 感染和 NDDs 统计数据：本系统综述在 PROSPERO 注册为 CRD42024554169。2024年7月26日进行了追溯注册。

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来源期刊

Italian Journal of Pediatrics PEDIATRICS-

CiteScore

6.10

自引率

13.90%

发文量

192

审稿时长

6-12 weeks

期刊介绍： Italian Journal of Pediatrics is an open access peer-reviewed journal that includes all aspects of pediatric medicine. The journal also covers health service and public health research that addresses primary care issues. The journal provides a high-quality forum for pediatricians and other healthcare professionals to report and discuss up-to-the-minute research and expert reviews in the field of pediatric medicine. The journal will continue to develop the range of articles published to enable this invaluable resource to stay at the forefront of the field. Italian Journal of Pediatrics, which commenced in 1975 as Rivista Italiana di Pediatria, provides a high-quality forum for pediatricians and other healthcare professionals to report and discuss up-to-the-minute research and expert reviews in the field of pediatric medicine. The journal will continue to develop the range of articles published to enable this invaluable resource to stay at the forefront of the field.