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学科主题: 精神卫生
题名:
Association study of an SNP combination pattern in the dopaminergic pathway in paranoid schizophrenia: a novel strategy for complex disorders
作者: Xu, Q1; Jia, YB1; Zhang, BY1; Zou, K1; Tao, YB1; Wang, YP1; Qiang, BQ1; Wu, GY1; Shen, Y1; Ji, HK1; Huang, Y1; Sun, XQ1; Ji, L1; Li, YD1; Yuan, YB1; Shu, L1; Yu, X1; Shen, YC1; Yu, YQ1; Ju, GZ1; Chinese Schizophrenia Consortium1
关键词: schizophrenia ; complex disorder ; susceptibility genotype combinations ; single nucleotide polymophism ; dopamine metabolic pathway ; clinial subgroup ; effective SNP combination pattern ; potential effective dynamic effects
刊名: MOLECULAR PSYCHIATRY
发表日期: 2004-05-01
DOI: 10.1038/sj.mp.4001472
卷: 9, 期:5, 页:510-521
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Neurosciences ; Psychiatry
研究领域[WOS]: Biochemistry & Molecular Biology ; Neurosciences & Neurology ; Psychiatry
关键词[WOS]: MONOAMINE-OXIDASE-A ; GENES ; SYSTEM ; NOREPINEPHRINE ; PHARMACOLOGY ; DYSFUNCTION ; BEHAVIOR ; SYMPTOMS ; GENETICS ; DISEASE
英文摘要:

Schizophrenia is a common mental disorder with a complex pattern of inheritance. Despite a large number of studies in the past decades, its molecular etiology remains unknown. In this study, we proposed a ′system-thinking′ strategy in seeking the combined effect of susceptibility genes for a complex disorder by using paranoid schizophrenia as an example. We genotyped 85 reported single-nucleotide polymorphisms (SNPs) present in 23 genes for the dopamine (DA) metabolism pathway among 83 paranoid schizophrenics and 108 normal controls with detailed clinical and genetic information. We developed two novel multilocus approaches - the potential effective SNP combination pattern and potential effective dynamic effects analysis, by which three susceptibility genotype combinations were found to be associated with schizophrenia. These results were also validated in a family-based cohort consisting of 95 family trios of paranoid schizophrenia. The present findings suggest that the COMT and ALDH3 combination may be the most common type involved in predisposing to schizophrenia. Since the combination blocks the whole pathways for the breakdown of DA and noradrenaline, it is very likely to play a central role in developing paranoid schizophrenia.

语种: 英语
WOS记录号: WOS:000221159300009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53052
Appears in Collections:北京大学精神卫生研究所_期刊论文

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作者单位: 1.Peking Univ, Inst Mental Hlth, Beijing 100871, Peoples R China
2.Natl Ctr Human Genome Res, Beijing, Peoples R China
3.Chinese Acad Med Sci, PUMC, Inst Basic Med Sci, Natl Lab Med Mol Biol, Beijing 100005, Peoples R China
4.Tsing Hua Univ, Dept Automat, Minist Educ Key Lab Bioinformat, State Key Lab Intelligent Technol & Syst, Beijing 100084, Peoples R China
5.Jilin Univ, Res Ctr Genom Med, Natl Ctr Human Genome Res, Changchun 130023, Jilin, Peoples R China

Recommended Citation:
Xu, Q,Jia, YB,Zhang, BY,et al. Association study of an SNP combination pattern in the dopaminergic pathway in paranoid schizophrenia: a novel strategy for complex disorders[J]. MOLECULAR PSYCHIATRY,2004,9(5):510-521.
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