ArticleBMC medicine2023
Reduced Vrk2 expression is associated with higher risk of depression in humans and mediates depressive-like behaviors in mice.
Article in BMC medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.
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Who cites it
5 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- Identification of 1q25.2 as a novel shared locus between schizophrenia and major depressive disorder in east Asians by integrative analyses.Translational psychiatry · 2025Pooled it
- Genetic mapping in collaborative cross mouse strains identifies loci that affect initial sensitivity to cocaine.Psychopharmacology · 2026Article
- USP11 drives stress-induced synaptic structural deficits and depression-like behaviors through GSK3β/mTOR signaling.Neurobiology of stress · 2026Article
- Optimization of potential targets for antidepressant Chinese medicines: AI and multi-omics methods.Chinese medicine · 2026Review
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundGenome-wide association studies (GWAS) have reported single-nucleotide polymorphisms (SNPs) in the VRK serine/threonine kinase 2 gene (VRK2) showing genome-wide significant associations with major depression, but the regulation effect of the risk SNPs on VRK2 as well as their roles in the illness are yet to be elucidated.
methodsBased on the summary statistics of major depression GWAS, we conducted population genetic analyses, epigenome bioinformatics analyses, dual luciferase reporter assays, and expression quantitative trait loci (eQTL) analyses to identify the functional SNPs regulating VRK2; we also carried out behavioral assessments, dendritic spine morphological analyses, and phosphorylated 4D-label-free quantitative proteomics analyses in mice with Vrk2 repression.
resultsWe identified a SNP rs2678907 located in the 5' upstream of VRK2 gene exhibiting large spatial overlap with enhancer regulatory marks in human neural cells and brain tissues. Using luciferase reporter gene assays and eQTL analyses, the depression risk allele of rs2678907 decreased enhancer activities and predicted lower VRK2 mRNA expression, which is consistent with the observations of reduced VRK2 level in the patients with major depression compared with controls. Notably, Vrk2
conclusionsVrk2 deficiency mice showed behavioral abnormalities that mimic human depressive phenotypes, which may serve as a useful murine model for studying the pathophysiology of depression.
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