Causal role of mitochondrial-related genes in autism spectrum disorder

WANG Jian; LIU Chang; LIN lin; NIU Tingting; ZHANG Jianying

doi:10.11852/zgetbjzz2024-1255

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Chinese Journal of Child Health Care ›› 2025, Vol. 33 ›› Issue (11) : 1212-1217. DOI: 10.11852/zgetbjzz2024-1255

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Causal role of mitochondrial-related genes in autism spectrum disorder

WANG Jian¹,LIU Chang²,LIN lin³,NIU Tingting¹,ZHANG Jianying¹

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Abstract

Objective To investigate the potential genetic mechanisms of mitochondrial-related genes in Autism Spectrum Disorder (ASD) using Summary-data-based Mendelian Randomization (SMR) and colocalization analysis based on multi-omics data. Methods Methylation quantitative trait loci (mQTLs), expression quantitative trait loci (eQTLs), and protein abundance quantitative trait loci (pQTLs) data were obtained from relevant QTL studies.The associations between mitochondrial-related genes and ASD were evaluated using SMR and colocalization analysis, and validated using datasets from FinnGen, UK Biobank (UKB), and the GWAS Catalog.The causal relationships between methylation, gene expression, and disease risk were further explored using SMR LocusPlot and SMR EffectPlot. Results The expression level of CHCHD3 was negatively associated with ASD risk (OR=0.27, 95%CI: 0.08-0.84).Lower methylation levels of NDUFA13 were associated with increased ASD risk, and upregulation of NDUFA13 expression increased ASD risk (OR=2.55, 95%CI: 1.03-6.28).Colocalization analysis further confirmed strong evidence for colocalization between the CHCHD3 methylation site (cg19918623) and multiple NDUFA13 methylation sites (cg03233793, cg07624705, cg25274157) with ASD risk (PP.H4 > 0.5). Conclusion Multi-omics evidence supports the potential association of mitochondrial-related genes CHCHD3 and NDUFA13 with ASD risk, providing new insights into the pathogenesis of ASD.

Key words

autism spectrum disorder / Mendelian randomization / mitochondrion / genetics / multi-omics level

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WANG Jian, LIU Chang, LIN lin, NIU Tingting, ZHANG Jianying. Causal role of mitochondrial-related genes in autism spectrum disorder[J]. Chinese Journal of Child Health Care. 2025, 33(11): 1212-1217 https://doi.org/10.11852/zgetbjzz2024-1255

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