ArticleMolecular psychiatry2022
A causal association of ANKRD37 with human hippocampal volume.
Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 9 citations in OpenAlex.
- DNA methylation signatures of bilateral hippocampal volume, asymmetry and atrophy: a cross-omics analysis in the general population.EBioMedicine · 2026Pooled it
- Computational whole-body-exposome models for global precision brain health.Nature communications · 2025Article
- Glabridin Improves Depression-Like Behaviors in Mice by Modulating Neuroinflammation via MAPK/NF-κB Signaling Pathway.Neurochemical research · 2025Article
- Research on the potential mechanisms and therapeutic drug for the co-occurrence of major depressive disorder in castration-resistant prostate cancer.Scientific reports · 2025Article
- Transcriptional Responses of Different Brain Cell Types to Oxygen Decline.Brain sciences · 2024Article
- Citalopram exposure of hESCs during neuronal differentiation identifies dysregulated genes involved in neurodevelopment and depression.Frontiers in cell and developmental biology · 2024Article
- The Alzheimer's Disease Neuroimaging Initiative in the era of Alzheimer's disease treatment: A review of ADNI studies from 2021 to 2022.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- Cortical connectivity gradients and local timescales during cognitive states are modulated by cognitive loads.Brain structure & function · 2022Article
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Authors and funding
32 authors at 16 institutions in 7 countries.
Funding
Abstract
Human hippocampal volume has been separately associated with single nucleotide polymorphisms (SNPs), DNA methylation and gene expression, but their causal relationships remain largely unknown. Here, we aimed at identifying the causal relationships of SNPs, DNA methylation, and gene expression that are associated with hippocampal volume by integrating cross-omics analyses with genome editing, overexpression and causality inference. Based on structural neuroimaging data and blood-derived genome, transcriptome and methylome data, we prioritized a possibly causal association across multiple molecular phenotypes: rs1053218 mutation leads to cg26741686 hypermethylation, thus leads to overactivation of the associated ANKRD37 gene expression in blood, a gene involving hypoxia, which may result in the reduction of human hippocampal volume. The possibly causal relationships from rs1053218 to cg26741686 methylation to ANKRD37 expression obtained from peripheral blood were replicated in human hippocampal tissue. To confirm causality, we performed CRISPR-based genome and epigenome-editing of rs1053218 homologous alleles and cg26741686 methylation in mouse neural stem cell differentiation models, and overexpressed ANKRD37 in mouse hippocampus. These in-vitro and in-vivo experiments confirmed that rs1053218 mutation caused cg26741686 hypermethylation and ANKRD37 overexpression, and cg26741686 hypermethylation favored ANKRD37 overexpression, and ANKRD37 overexpression reduced hippocampal volume. The pairwise relationships of rs1053218 with hippocampal volume, rs1053218 with cg26741686 methylation, cg26741686 methylation with ANKRD37 expression, and ANKRD37 expression with hippocampal volume could be replicated in an independent healthy young (n = 443) dataset and observed in elderly people (n = 194), and were more significant in patients with late-onset Alzheimer's disease (n = 76). This study revealed a novel causal molecular association mechanism of ANKRD37 with human hippocampal volume, which may facilitate the design of prevention and treatment strategies for hippocampal impairment.
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