Genetically predicted causal effects between cytomegalovirus infection and neurodevelopmental disorders

LAI Qiankun; LI Yinzhi; HUANG Qi; GUO Jingmin; YAO Qingshan

doi:10.11852/zgetbjzz2025-0416

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Chinese Journal of Child Health Care ›› 2025, Vol. 33 ›› Issue (12) : 1316-1322. DOI: 10.11852/zgetbjzz2025-0416

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Genetically predicted causal effects between cytomegalovirus infection and neurodevelopmental disorders

LAI Qiankun, LI Yinzhi, HUANG Qi, GUO Jingmin, YAO Qingshan

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Abstract

Objective To investigate the causal relationship between cytomegalovirus (CMV) infection and neurodevelopmental disorders (NDDs) in children,in order to provide evidence for targeted intervention. Methods Using genome-wide association study (GWAS) data, a two-sample Mendelian randomization (TSMR) approach was employed to analyze causal associations between four CMV antibodies and autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), developmental intellectual disability (DID), and tic disorder (TD). The inverse variance weighted (IVW) method was primarily used for causal effect estimation, with Bonferroni correction applied to determine significance thresholds. Robustness of Results was validated via Cochran′s Q test, MR-Egger regression intercept, MR-PRESSO, and leave-one-out analysis. Reverse MR was conducted to exclude reverse causality. Results TSMR analysis under Bonferroni correction revealed a significant positive causal relationship between anti-CMV IgG and ASD risk (OR=1.333, 95%CI:1.103 - 1.611, P=0.003), indicating that CMV infection significantly increased ASD risk. No causal associations were found between CMV antibodies and ADHD, DID, or TD. Cochran′s Q test confirmed no heterogeneity, MR-Egger regression indicated no horizontal pleiotropy, MR-PRESSO detected no outliers, and leave-one-out analysis supported result reliability. Reverse MR excluded reverse causality. Conclusion This Mendelian randomization study confirms a genetically predicted positive causal link between CMV infection and ASD risk, suggesting that perinatal CMV prevention may hold potential value for reducing ASD risk.

Key words

cytomegalovirus / neurodevelopmental disorders / autism spectrum disorder / Mendelian randomization

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LAI Qiankun, LI Yinzhi, HUANG Qi, GUO Jingmin, YAO Qingshan. Genetically predicted causal effects between cytomegalovirus infection and neurodevelopmental disorders[J]. Chinese Journal of Child Health Care. 2025, 33(12): 1316-1322 https://doi.org/10.11852/zgetbjzz2025-0416

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