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ALDH2 Glu504Lys Confers Susceptibility to Schizophrenia and Impacts Hippocampal-Prefrontal Functional Connectivity
Zheng, Fanfan1,3,6,7; Yan, Hao3,6,7; Liu, Bing1,2; Yue, Weihua3,6,7; Fan, Lingzhong1; Liao, Jinmin3,6,7; Cui, Yue1,2; Lu, Tianlan3,6,7; Jiang, Tianzi1,2,8,9; Zhang, Dai3,4,5,6,7; Tianzi Jiang
Source PublicationCEREBRAL CORTEX
AbstractAlthough 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.
Other Abstract英文摘要 
KeywordFunctional Connectivity Glu504lys Hippocampus Pfc Schizophrenia
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI ; SSCI
Funding OrganizationNational Key Basic Research and Development Program (973 Program)(2011CB707800) ; National Key Technology R&D Program of China(2015BAI13B01) ; Strategic Priority Research Program of the Chinese Academy of Sciences(XDB02030300) ; Natural Science Foundation of China(81361120395 ; 91232305 ; 91432304 ; 81370032 ; 81222017 ; 91132301 ; 91232718)
WOS Research AreaNeurosciences & Neurology
WOS SubjectNeurosciences
WOS IDWOS:000397636600027
Citation statistics
Cited Times:3[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Corresponding AuthorTianzi Jiang
Affiliation1.Chinese Acad Sci, Brainnetome Ctr, Beijing, Peoples R China
2.Chinese Acad Sci, Natl Lab Pattern Recognit, Inst Automat, Beijing, Peoples R China
3.Peking Univ, Inst Mental Hlth, Hosp 6, Beijing, Peoples R China
4.Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing, Peoples R China
5.Peking Univ, PKU IDG McGovern Inst Brain Res, Beijing, Peoples R China
6.Peking Univ, Minist Hlth, Key Lab Mental Hlth, Beijing, Peoples R China
7.Peking Univ, Natl Clin Res Ctr Mental Disorders, Beijing, Peoples R China
8.Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia
9.Univ Elect Sci & Technol China, Sch Life Sci & Technol, Key Lab NeuroInformat, Minist Educ, Chengdu, Peoples R China
Recommended Citation
GB/T 7714
Zheng, Fanfan,Yan, Hao,Liu, Bing,et al. ALDH2 Glu504Lys Confers Susceptibility to Schizophrenia and Impacts Hippocampal-Prefrontal Functional Connectivity[J]. CEREBRAL CORTEX,2017,27(3):2034-2040.
APA Zheng, Fanfan.,Yan, Hao.,Liu, Bing.,Yue, Weihua.,Fan, Lingzhong.,...&Tianzi Jiang.(2017).ALDH2 Glu504Lys Confers Susceptibility to Schizophrenia and Impacts Hippocampal-Prefrontal Functional Connectivity.CEREBRAL CORTEX,27(3),2034-2040.
MLA Zheng, Fanfan,et al."ALDH2 Glu504Lys Confers Susceptibility to Schizophrenia and Impacts Hippocampal-Prefrontal Functional Connectivity".CEREBRAL CORTEX 27.3(2017):2034-2040.
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