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Association study of an SNP combination pattern in the dopaminergic pathway in paranoid schizophrenia: a novel strategy for complex disorders
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
2004-05-01
DOI10.1038/sj.mp.4001472
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
引用统计
被引频次:28[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/53052
专题北京大学精神卫生研究所
北京大学第三临床医学院_感染疾病科
北京大学口腔医学院_财务处
北京大学精神卫生研究所_精神科
北京大学精神卫生研究所_护理部
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
推荐引用方式
GB/T 7714
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.
APA Xu, Q.,Jia, YB.,Zhang, BY.,Zou, K.,Tao, YB.,...&Chinese Schizophrenia Consortium.(2004).Association study of an SNP combination pattern in the dopaminergic pathway in paranoid schizophrenia: a novel strategy for complex disorders.MOLECULAR PSYCHIATRY,9(5),510-521.
MLA Xu, Q,et al."Association study of an SNP combination pattern in the dopaminergic pathway in paranoid schizophrenia: a novel strategy for complex disorders".MOLECULAR PSYCHIATRY 9.5(2004):510-521.
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