ALDH2 Glu504Lys Confers Susceptibility to Schizophrenia and Impacts   Hippocampal-Prefrontal Functional Connectivity

doi:10.1093/cercor/bhw056

CORC > 北京大学 > 生命科学学院

	ALDH2 Glu504Lys Confers Susceptibility to Schizophrenia and Impacts Hippocampal-Prefrontal Functional Connectivity
	Zheng, Fanfan ; Yan, Hao ; Liu, Bing ; Yue, Weihua ; Fan, Lingzhong ; Liao, Jinmin ; Cui, Yue ; Lu, Tianlan ; Jiang, Tianzi ; Zhang, Dai
刊名	CEREBRAL CORTEX
	2017
关键词	functional connectivity Glu504Lys hippocampus PFC schizophrenia INDIVIDUAL-DIFFERENCES GENETIC ASSOCIATION OXIDATIVE STRESS WORKING-MEMORY CORTEX METAANALYSIS RISK POLYMORPHISM INTEGRATION METABOLISM
DOI	10.1093/cercor/bhw056
英文摘要	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.; National 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]; SCI(E); PubMed; SSCI; ARTICLE; 3; 2034-2040; 27
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/434639]
专题	生命科学学院心理与认知科学学院
推荐引用方式 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.
APA	Zheng, Fanfan.,Yan, Hao.,Liu, Bing.,Yue, Weihua.,Fan, Lingzhong.,...&Zhang, Dai.(2017).ALDH2 Glu504Lys Confers Susceptibility to Schizophrenia and Impacts Hippocampal-Prefrontal Functional Connectivity.CEREBRAL CORTEX.
MLA	Zheng, Fanfan,et al."ALDH2 Glu504Lys Confers Susceptibility to Schizophrenia and Impacts Hippocampal-Prefrontal Functional Connectivity".CEREBRAL CORTEX (2017).