Evidence map›Paper›PMID 42308296›Full record

ArticleScience advances2026

Haplotype-resolved methylomes reveal parent-of-origin DNA methylation imbalance in autism spectrum disorder.

Lu Xia, Hailiang Guo, Ruiting Liu, Xue Ren, Shaohuai Han, Xu Huang, Ying Peng, Yan Zhu, Yuanfeng Huang, Zhaowei Jiang and 22 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

32 authors.

Lu XiaCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008 Hunan, China.ORCID 0000-0003-2450-1320
Hailiang GuoSchool of Public Health, Peking University, Beijing 100191, China.ORCID 0009-0005-7645-189X
Ruiting LiuCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008 Hunan, China.ORCID 0009-0000-7397-3848
Xue RenAnnoroad Gene Technology (Beijing) Co. Ltd, Beijing 100176, China.ORCID 0009-0006-4227-7368
Shaohuai HanAnnoroad Gene Technology (Beijing) Co. Ltd, Beijing 100176, China.ORCID 0009-0005-2186-1074
Xu HuangCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008 Hunan, China.
Ying PengCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008 Hunan, China.ORCID 0000-0002-7760-0317
Yan ZhuCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008 Hunan, China.
Yuanfeng HuangBioinformatics Center, National Clinical Research Center for Geriatric Diseases, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China.
Zhaowei JiangCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008 Hunan, China.
Tengfei ZhuThe Key Laboratory of Pediatric Rare Diseases of the Ministry of Education, University of South China, Hengyang and Central South University, Changsha, 410078 Hunan, China.
Tengfei LuoCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008 Hunan, China.
Zhikun WangCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008 Hunan, China.ORCID 0009-0007-2811-9141
Xun ZhouAnnoroad Gene Technology (Beijing) Co. Ltd, Beijing 100176, China.ORCID 0009-0005-8738-1081
Xiaobo LiAnnoroad Gene Technology (Beijing) Co. Ltd, Beijing 100176, China.ORCID 0000-0002-4984-0081
Yanping ZhuCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008 Hunan, China.
Ting BaiCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008 Hunan, China.
Qi TianCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008 Hunan, China.ORCID 0000-0003-0798-2759
Zhiqing HuThe Key Laboratory of Pediatric Rare Diseases of the Ministry of Education, University of South China, Hengyang and Central South University, Changsha, 410078 Hunan, China.ORCID 0000-0002-3334-2002
Miaojin ZhouThe Key Laboratory of Pediatric Rare Diseases of the Ministry of Education, University of South China, Hengyang and Central South University, Changsha, 410078 Hunan, China.ORCID 0000-0002-6636-6000
Qian JiangKey Laboratory of Hunan Province in Neurodegenerative Disorders, Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410078 Hunan, China.
Yidong ShenMental Health Institute, The Second Xiangya Hospital of Central South University, Changsha, 410011 Hunan, China.
Jianjun OuMental Health Institute, The Second Xiangya Hospital of Central South University, Changsha, 410011 Hunan, China.ORCID 0000-0002-0611-7715
Yixiao ZhuBioinformatics Center, National Clinical Research Center for Geriatric Diseases, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China.ORCID 0000-0002-8558-2120
Qiao ZhouBioinformatics Center, National Clinical Research Center for Geriatric Diseases, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China.
Qian PanCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008 Hunan, China.
Tianyun WangDepartment of Medical Genetics, Center for Medical Genetics, School of Basic Medical Sciences, Peking University, Beijing, China.ORCID 0000-0002-5179-087X
Hui GuoCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008 Hunan, China.ORCID 0000-0002-1570-2545
Beisha TangHengyang Medical School, University of South China, Hengyang, 421001 Hunan, China.ORCID 0000-0003-2120-1576
Zhengmao HuCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008 Hunan, China.ORCID 0009-0004-4181-5692
Jinchen LiBioinformatics Center, National Clinical Research Center for Geriatric Diseases, Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China.ORCID 0000-0001-5522-806X
Kun XiaCenter for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, 410008 Hunan, China.ORCID 0000-0001-8090-6002

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Epigenetic dysregulation plays an essential role in autism spectrum disorder (ASD), but the parent-of-origin effects (POEs) of DNA methylation remain unknown. Here, we applied PacBio HiFi sequencing with haplotype-phased methylation profiling in 124 individuals (31 ASD quartets) to systematically dissect POE-dependent methylation. Comparative analysis of phased methylomes between probands and unaffected siblings identified 114 paternal- and 106 maternal-specific differential methylated cytosines (DMCs), 45 and 46 differential methylated regions (DMRs), and 2425 and 2693 methylation outliers (MOs), respectively. These POE methylation alterations were enriched in ASD-relevant gene categories but exhibited distinct genomic distributions and functional pathways between parental haplotypes. Furthermore, genome-wide parent-of-origin DMR analysis identified 443 allele-specific methylation (ASM) regions, from which we detected 34 differential expression ASMs and 62 ASM outliers, showing pronounced enrichment within PWS/AS locus and ASD-associated genes. Collectively, this study provides a comprehensive evidence of pervasive POE-dependent methylation imbalance and aberrant ASM at imprinting regions underlying ASD pathogenesis, offering insights into epigenetic mechanisms of complex neurodevelopmental disorders.

Indexed as

Autism Spectrum DisorderDNA MethylationEpigenomeHaplotypesAllelesEpigenesis, GeneticFemaleGenomic ImprintingHumansMale

Identifiers

PMID42308296
PMCPMC13274601

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