Title: ALDH2 Glu504Lys Confers Susceptibility to Schizophrenia and Impacts Hippocampal-Prefrontal Functional Connectivity
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| Authors: Zheng, FF; Yan, H; Liu, B; Yue, WH; Fan, LZ; Liao, JM; Cui, Y; Lu, TL; Jiang, TZ; Zhang, D
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| Author Full Names: Zheng, Fanfan; Yan, Hao; Liu, Bing; Yue, Weihua; Fan, Lingzhong; Liao, Jinmin; Cui, Yue; Lu, Tianlan; Jiang, Tianzi; Zhang, Dai
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| Source: CEREBRAL CORTEX, 27 (3):2034-2040; 10.1093/cercor/bhw056 MAR 2017
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| Language: English
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| 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.
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| ISSN: 1047-3211
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| eISSN: 1460-2199
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| IDS Number: EP8PF
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| Unique ID: WOS:000397636600027
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