| Title | ALDH2 Glu504Lys Confers Susceptibility to Schizophrenia and Impacts Hippocampal-Prefrontal Functional Connectivity |
| Authors | Zheng, Fanfan Yan, Hao Liu, Bing Yue, Weihua Fan, Lingzhong Liao, Jinmin Cui, Yue Lu, Tianlan Jiang, Tianzi Zhang, Dai |
| Affiliation | Chinese Acad Sci, Brainnetome Ctr, Beijing, Peoples R China. Chinese Acad Sci, Natl Lab Pattern Recognit, Inst Automat, Beijing, Peoples R China. Peking Univ, Inst Mental Hlth, Hosp 6, Beijing, Peoples R China. Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing, Peoples R China. Peking Univ, PKU IDG McGovern Inst Brain Res, Beijing, Peoples R China. Peking Univ, Minist Hlth, Key Lab Mental Hlth, Beijing, Peoples R China. Peking Univ, Natl Clin Res Ctr Mental Disorders, Beijing, Peoples R China. Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia. Univ Elect Sci & Technol China, Sch Life Sci & Technol, Key Lab NeuroInformat, Minist Educ, Chengdu, Peoples R China. Chinese Acad Sci, Brainnetome Ctr, Inst Automat, 95 Zhong Guan Cun East Rd, Beijing 100190, Peoples R China. Zhang, D (reprint author), Peking Univ, Inst Mental Hlth, 51 Hua Yuan Bei Rd, Beijing 100191, Peoples R China. |
| Keywords | functional connectivity Glu504Lys hippocampus PFC schizophrenia INDIVIDUAL-DIFFERENCES GENETIC ASSOCIATION OXIDATIVE STRESS WORKING-MEMORY CORTEX METAANALYSIS RISK POLYMORPHISM INTEGRATION METABOLISM |
| Issue Date | 2017 |
| Publisher | CEREBRAL CORTEX |
| Citation | CEREBRAL CORTEX.2017,27(3),2034-2040. |
| Abstract | Although previous evidence suggested that ALDH2 is a candidate gene for schizophrenia, the association and underlying mechanisms have never been investigated. Therefore, we investigated ALDH2 as a susceptibility gene for schizophrenia and explored the effect of its polymorphisms on brain functions. In the discovery stage, we detected a positive association between a dominant-negative mutant, Glu504Lys, and schizophrenia (P = 8.01E-5, OR = 1.34, 95% CI = 1.16-1.55). This association was confirmed in the validation stage (P = 3.48E-6, OR = 1.28, 95% CI = 1.15-1.42). The combined P reached a genome-wide significance (P-combined = 1.32E-9, OR = 1.30, 95% CI = 1.20-1.42). To investigate the neural mechanism linking Glu504Lys to schizophrenia, we calculated the functional connectivity (FC) and applied an imaging genetics strategy using resting-state fMRI data. The imaging analysis revealed a significant interaction of diagnostic group by genotype for FC between the left hippocampus and the prefrontal cortex. In the Glu homozygotes, hippocampal-prefrontal FC correlated inversely with memory performance in the healthy controls and with the PANSS negative score in the schizophrenia patients. Our results supported a role for ALDH2 in the pathophysiology of schizophrenia. Moreover, variation at Glu504Lys disrupts hippocampal-prefrontal FC, which might be the neural mechanism linking it to the disease. |
| URI | http://hdl.handle.net/20.500.11897/434639 |
| ISSN | 1047-3211 |
| DOI | 10.1093/cercor/bhw056 |
| Indexed | SCI(E) PubMed SSCI |
| Appears in Collections: | 第六医院 生命科学学院 心理与认知科学学院 |
