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

doi:10.1093/cercor/bhw056

	ALDH2 Glu504Lys Confers Susceptibility to Schizophrenia and Impacts Hippocampal-Prefrontal Functional Connectivity
	Zheng, Fanfan1,3,6,7 ; Yan, Hao 3,6,7; Liu, Bing1,2 ; Yue, Weihua 3,6,7; Fan, Lingzhong1 ; Liao, Jinmin 3,6,7; Cui, Yue1,2 ; Lu, Tianlan 3,6,7; Jiang, Tianzi1,2,8,9 ; Zhang, Dai 3,4,5,6,7
刊名	CEREBRAL CORTEX
	2017-03-01
卷号	27 期号:3 页码:2034-2040
关键词	Functional Connectivity Glu504lys Hippocampus Pfc Schizophrenia
DOI	10.1093/cercor/bhw056
文献子类	Article
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.
WOS关键词	INDIVIDUAL-DIFFERENCES ; GENETIC ASSOCIATION ; OXIDATIVE STRESS ; WORKING-MEMORY ; CORTEX ; METAANALYSIS ; RISK ; POLYMORPHISM ; INTEGRATION ; METABOLISM
WOS研究方向	Neurosciences & Neurology
语种	英语
WOS记录号	WOS:000397636600027
资助机构	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)
内容类型	期刊论文
源URL	[http://ir.ia.ac.cn/handle/173211/12122]
专题	自动化研究所_脑网络组研究中心
通讯作者	Tianzi Jiang
作者单位	1.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
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,2017,27(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.