ArticleMolecular psychiatry2014
Convergent lines of evidence support CAMKK2 as a schizophrenia susceptibility gene.
Article in Molecular psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.
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Who cites it
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 56 citations in OpenAlex.
- Genetic association and meta-analysis of a schizophrenia GWAS variant rs10489202 in East Asian populations.Translational psychiatry · 2018Pooled it
- The Gene Encoding Protocadherin 9 (PCDH9), a Novel Risk Factor for Major Depressive Disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Pooled it
- Loss of CAMKK2 and iron-transport proteins-transferrin and its receptor-in the Alzheimer's disease hippocampus: link to tau pathology.Frontiers in cell and developmental biology · 2026Article
- Loss of calcium/calmodulin-dependent protein kinase kinase 2, transferrin, and transferrin receptor proteins in the temporal cortex of Alzheimer's patients postmortem is associated with abnormal iron homeostasis: implications for patient survival.Frontiers in cell and developmental biology · 2024Article
- CaMKK2 as an emerging treatment target for bipolar disorder.Molecular psychiatry · 2023Review
- Metabolic regulation to treat bipolar depression: mechanisms and targeting by trimetazidine.Molecular psychiatry · 2023Review
- SGC-CAMKK2-1: A Chemical Probe for CAMKK2.Cells · 2023Article
- Molecular Mechanisms Underlying CaInternational journal of molecular sciences · 2022Review
- Motor Stereotypic Behavior Was Associated With Immune Response in Macaques: Insight From Transcriptome and Gut Microbiota Analysis.Frontiers in microbiology · 2021Article
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- Expression Analysis of CYFIP1 and CAMKK2 Genes in the Blood of Epileptic and Schizophrenic Patients.Journal of molecular neuroscience : MN · 2018Article
- Further evidence for the genetic association betweenHereditas · 2018Article
- Common and Rare Genetic Risk Factors Converge in Protein Interaction Networks Underlying Schizophrenia.Frontiers in genetics · 2018Article
- Identification of a Bipolar Disorder Vulnerable Gene CHDH at 3p21.1.Molecular neurobiology · 2017Article
- Progress in genome-wide association studies of schizophrenia in Han Chinese populations.NPJ schizophrenia · 2017Review
- The schizophrenia risk gene ZNF804A: clinical associations, biological mechanisms and neuronal functions.Molecular psychiatry · 2017Review
- Impact of Genetic Variation on Human CaMKK2 Regulation by CaScientific reports · 2017Article
- Convergent Lines of Evidence Support LRP8 as a Susceptibility Gene for Psychosis.Molecular neurobiology · 2016Article
- Effect of rs1063843 in the CAMKK2 gene on the dorsolateral prefrontal cortex.Human brain mapping · 2016Article
Corrections and comments
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Authors and funding
41 authors at 20 institutions in 12 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genes that are differentially expressed between schizophrenia patients and healthy controls may have key roles in the pathogenesis of schizophrenia. We analyzed two large-scale genome-wide expression studies, which examined changes in gene expression in schizophrenia patients and their matched controls. We found calcium/calmodulin (CAM)-dependent protein kinase kinase 2 (CAMKK2) is significantly downregulated in individuals with schizophrenia in both studies. To seek the potential genetic variants that may regulate the expression of CAMKK2, we investigated the association between single-nucleotide polymorphisms (SNPs) within CAMKK2 and the expression level of CAMKK2. We found one SNP, rs1063843, which is located in intron 17 of CAMKK2, is strongly associated with the expression level of CAMKK2 in human brains (P=1.1 × 10(-6)) and lymphoblastoid cell lines (the lowest P=8.4 × 10(-6)). We further investigated the association between rs1063843 and schizophrenia in multiple independent populations (a total of 130 623 subjects) and found rs1063843 is significantly associated with schizophrenia (P=5.17 × 10(-5)). Interestingly, we found the T allele of rs1063843, which is associated with lower expression level of CAMKK2, has a higher frequency in individuals with schizophrenia in all of the tested samples, suggesting rs1063843 may be a causal variant. We also found that rs1063843 is associated with cognitive function and personality in humans. In addition, protein-protein interaction (PPI) analysis revealed that CAMKK2 participates in a highly interconnected PPI network formed by top schizophrenia genes, which further supports the potential role of CAMKK2 in the pathogenesis of schizophrenia. Taken together, these converging lines of evidence strongly suggest that CAMKK2 may have pivotal roles in schizophrenia susceptibility.
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