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SubjectsArfgengi (1)Genamengi (1)
Geðklofi (1)
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Molecular psychiatry (1)
AuthorsAlkelai, A (1)Chen, C (1)
Cichon, S (1)
College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, China [2] Department of Ophthalmology and Flaum Eye Institute, University of Rochester, Rochester, NY, USA. 2Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA. 31] Nanchang University, Nanchang, China [2] Gannan Medical University, Ganzhou, China [3] Jiangxi Provincial People's Hospital, Nanchang, China. 4deCODE Genetics, Reykjavik, Iceland. 5Department of Biomedicine, Aarhus University, Aarhus C, Denmark. 6College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, China. 7Neuropsychiatric Genetics Group and Department of Psychiatry, Institute of Molecular Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, St James Hospital, Dublin, Ireland. 8Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China. 9Department of Psychology and Social Behavior, University of California, Irvine, CA, USA. 101] Institute of Mental Health, Peking University, Beijing, China [2] Key Laboratory of Mental Health, Ministry of Health (Peking University), Beijing, China. 11Department of Psychiatry, Biological Psychiatry Laboratory, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 12Department of Psychiatry, the First Teaching Hospital of Xinjiang Medical University, Urumqi, China. 13Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, University of Mannheim, Mannheim, Germany. 14Department of Genomics, Life and Brain Center, and Institute of Human Genetics, University of Bonn, Bonn, Germany. 151] Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College, London, UK [2] Eli Lilly and Co. Ltd, Erl Wood Manor, Surrey, UK. 16Section of Psychiatry, University of Verona, Verona, Italy. 17Mental Health and Substance Abuse Services, National Institute for Health and Welfare THL, Helsinki, Finland. 181] Division of Molecular and Clinical Neurobiology, Department of Psychiatry, Ludwig-Maximilians University, Munich, Germany [2] Department of Psychiatry, University of Halle-Wittenberg, Halle, Germany. 19Mental Health Research Center, Russian Academy of Medical Sciences, Moscow, Russia. 20Department of Psychiatry and Drug Addiction, Tbilisi State Medical University (TSMU), Tbilisi, Georgia. 21Department of Child and Adolescent Psychiatry, University of Skopje, Skopje, Macedonia. 22Medical Faculty, University of Belgrade, Belgrade, Serbia. 23Department of Psychiatry and Psychotherapy, University Medical Center Georg-August-Universität, Goettingen, Germany. 24State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing, China. 25Department of Biological Chemistry, University of California, Irvine, CA, USA. 261] deCODE Genetics, Reykjavik, Iceland [2] School of Medicine, University of Iceland, Reykjavik, Iceland. 271] School of Medicine, University of Iceland, Reykjavik, Iceland [2] Department of Psychiatry, National University Hospital, Reykjavik, Iceland. 28Affiliated Eye Hospital of Nanchang University, Nanchang, China. 29State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. (1)Collier, D A (1)View MoreTypesArticle (1)

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Convergent lines of evidence support CAMKK2 as a schizophrenia susceptibility gene.

Luo, X-J; Li, M; Huang, L; Steinberg, S; Mattheisen, M; Liang, G; Donohoe, G; Shi, Y; Chen, C; Yue, W; et al. (Nature Publishing Group, 2014-07)
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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