دورية أكاديمية
Convergent lines of evidence support CAMKK2 as a schizophrenia susceptibility gene
| العنوان: | Convergent lines of evidence support CAMKK2 as a schizophrenia susceptibility gene |
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| المؤلفون: | Luo, X-j, Li, M., Huang, L., Steinberg, S., Mattheisen, M., Liang, G., Donohoe, G., Shi, Y., Chen, C., Yue, W., Alkelai, A., Lerer, B., Li, Z., Yi, Q., Rietschel, M., Cichon, S., Collier, D. A., Tosato, S., Suvisaari, J., Rujescu, Dan, Golimbet, V., Silagadze, T., Durmishi, N., Milovancevic, M. P., Stefansson, H., Schulze, T. G., Noethen, M. M., Lyne, R., Morris, D. W., Gill, M., Corvin, A., Zhang, D., Dong, Q., Moyzis, R. K., Stefansson, K., Sigurdsson, E., Hu, F., Su, B., Gan, L. |
| المساهمون: | Luo, XJ (reprint author), Univ Rochester, Dept Ophthalmol, Rochester, NY 14642 USA., Hangzhou Normal Univ, Coll Life & Environm Sci, Hangzhou, Zhejiang, Peoples R China., Univ Rochester, Dept Ophthalmol, Rochester, NY 14642 USA., Univ Rochester, Flaum Eye Inst, Rochester, NY 14642 USA., Lieber Inst Brain Dev, Baltimore, MD USA., Nanchang Univ, Nanchang, Peoples R China., Gannan Med Univ, Ganzhou, Peoples R China., Jiangxi Prov Peoples Hosp, Nanchang, Peoples R China., deCODE Genet, Reykjavik, Iceland., Aarhus Univ, Dept Biomed, Aarhus C, Denmark., St James Hosp, Univ Dublin Trinity Coll, Neuropsychiat Genet Grp, Dublin 8, Ireland., St James Hosp, Univ Dublin Trinity Coll, Inst Mol Med, Dept Psychiat, Dublin 8, Ireland., St James Hosp, Univ Dublin Trinity Coll, Trin Coll Inst Neurosci, Dublin 8, Ireland., Shanghai Jiao Tong Univ, Minist Educ, Key Lab Genet Dev & Neuropsychiat Disorders, Bio X Inst, Shanghai 200030, Peoples R China., Univ Calif Irvine, Dept Psychol & Social Behav, Irvine, CA USA., Peking Univ, Inst Mental Hlth, Beijing 100871, Peoples R China., Peking Univ, Minist Hlth, Key Lab Mental Hlth, Beijing 100871, Peoples R China., Hadassah Hebrew Univ, Med Ctr, Biol Psychiat Lab, Dept Psychiat, Jerusalem, Israel., Xinjiang Med Univ, Teaching Hosp 1, Dept Psychiat, Urumqi, Peoples R China., Univ Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-68131 Mannheim, Germany., Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany., Univ Bonn, Inst Human Genet, Bonn, Germany., Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Res Ctr, London, England., Eli Lilly & Co Ltd, Surrey, England., Univ Verona, Sect Psychiat, I-37100 Verona, Italy., Natl Inst Hlth & Welf THL, Mental Hlth & Substance Abuse Serv, Helsinki, Finland., Univ Munich, Dept Psychiat, Div Mol & Clin Neurobiol, D-80539 Munich, Germany., Univ Halle Wittenberg, Dept Psychiat, D-06108 Halle, Germany., Russian Acad Med Sci, Mental Hlth Res Ctr, Moscow 109801, Russia., TSMU, Dept Psychiat & Drug Addict, Tbilisi, Rep of Georgia., Univ Skopje, Dept Child & Adolescent Psychiat, Skopje, Macedonia., Univ Belgrade, Fac Med, Belgrade, Serbia., Univ Gottingen, Univ Med Ctr, Dept Psychiat & Psychotherapy, D-37073 Gottingen, Germany., Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China., Univ Calif Irvine, Dept Biol Chem, Irvine, CA USA., Univ Iceland, Sch Med, Reykjavik, Iceland., Natl Univ Hosp Reykjavik, Dept Psychiat, Reykjavik, Iceland., Nanchang Univ, Affiliated Eye Hosp, Nanchang, Peoples R China., Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming, Peoples R China. |
| المصدر: | SCI ; PubMed |
| بيانات النشر: | 分子精神病学 |
| سنة النشر: | 2014 |
| المجموعة: | Peking University Institutional Repository (PKU IR) / 北京大学机构知识库 |
| مصطلحات موضوعية: | association, CAMKK2, eQTL, expression, protein-protein interaction, schizophrenia, LONG-TERM-MEMORY, FUNCTIONAL GENOMICS APPROACH, PROTEIN-KINASE KINASE, BIPOLAR DISORDER, COMMON VARIANTS, PREFRONTAL CORTEX, WIDE ASSOCIATION, CONFERRING RISK, CANDIDATE GENES, MOLECULAR-CLONING |
| الوصف: | 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 x 10(-6)) and lymphoblastoid cell lines (the lowest P = 8.4 x 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 x 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. ; Biochemistry & Molecular Biology ; Neurosciences ; Psychiatry ; SCI(E) ; PubMed ; 6 ; ARTICLE ; Xiongjian_Luo@urmc.rochester.edu; Lin_Gan@URMC.Rochester.edu ; 7 ; 774-783 ; 19 |
| نوع الوثيقة: | journal/newspaper |
| اللغة: | English |
| تدمد: | 1359-4184 1476-5578 |
| العلاقة: | MOLECULAR PSYCHIATRY.2014,19,(7),774-783.; 656213; http://hdl.handle.net/20.500.11897/342787Test; WOS:000338185300006 |
| DOI: | 10.1038/mp.2013.103 |
| الإتاحة: | https://doi.org/20.500.11897/342787Test https://doi.org/10.1038/mp.2013.103Test https://hdl.handle.net/20.500.11897/342787Test |
| رقم الانضمام: | edsbas.FD0F1736 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 13594184 14765578 |
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| DOI: | 10.1038/mp.2013.103 |