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学科主题: 药物依赖
题名:
A Novel, Functional and Replicable Risk Gene Region for Alcohol Dependence Identified by Genome-Wide Association Study
作者: Zuo, Lingjun1,2; Zhang, Clarence K.3; Wang, Fei1,4; Li, Chiang-Shan R.1; Zhao, Hongyu3; Lu, Lingeng3; Zhang, Xiang-Yang5; Lu, Lin6; Zhang, Heping3; Zhang, Fengyu7; Krystal, John H.1,2; Luo, Xingguang1,2
刊名: PLOS ONE
发表日期: 2011-11-07
DOI: 10.1371/journal.pone.0026726
卷: 6, 期:11
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
研究领域[WOS]: Science & Technology - Other Topics
关键词[WOS]: POLYMORPHISMS ; POPULATION ; EXPRESSION ; FINGER
英文摘要:

Several genome-wide association studies (GWASs) reported tens of risk genes for alcohol dependence, but most of them have not been replicated or confirmed by functional studies. The present study used a GWAS to search for novel, functional and replicable risk gene regions for alcohol dependence. Associations of all top-ranked SNPs identified in a discovery sample of 681 African-American (AA) cases with alcohol dependence and 508 AA controls were retested in a primary replication sample of 1,409 European-American (EA) cases and 1,518 EA controls. The replicable associations were then subjected to secondary replication in a sample of 6,438 Australian family subjects. A functional expression quantitative trait locus (eQTL) analysis of these replicable risk SNPs was followed-up in order to explore their cis-acting regulatory effects on gene expression. We found that within a 90 Mb region around PHF3-PTP4A1 locus in AAs, a linkage disequilibrium (LD) block in PHF3-PTP4A1 formed the only peak associated with alcohol dependence at p<10(-4). Within this block, 30 SNPs associated with alcohol dependence in AAs (1.6x10(-5) <= p <= 0.050) were replicated in EAs (1.3x10(-3)<= p <= 0.038), and 18 of them were also replicated in Australians (1.8x10(-3)<= p <= 0.048). Most of these risk SNPs had strong cis-acting regulatory effects on PHF3-PTP4A1 mRNA expression across three HapMap samples. The distributions of -log(p) values for association and functional signals throughout this LD block were highly consistent across AAs, EAs, Australians and three HapMap samples. We conclude that the PHF3-PTP4A1 region appears to harbor a causal locus for alcohol dependence, and proteins encoded by PHF3 and/or PTP4A1 might play a functional role in the disorder.

语种: 英语
所属项目编号: K01 DA029643 ; K24 DA017899 ; R01 DA016750 ; K02 DA026990 ; R01 DA013423 ; R01 AA016015 ; R21 AA020319 ; R21 AA018004 ; K24 AA013736 ; R01 AA11330 ; R01 AA017535 ; P50 AA012870 ; U10 AA008401 ; 17616 ; U01 HG004422 ; U01HG004438 ; U01 HG004446 ; P01 CA089392 ; HHSN268200782096C
项目资助者: National Institute on Drug Abuse (NIDA) ; National Institute on Alcohol Abuse and Alcoholism (NIAAA) ; National Alliance for Research on Schizophrenia and Depression (NARSAD) Award ; Department of Veterans Affairs through VA Alcohol Research Center ; VA National Center for PTSD ; Depression REAP ; National Institutes of Health (NIH) Genes, Environment and Health Initiative (GEI) ; GENEVA Coordinating Center ; National Cancer Institute ; NIH
WOS记录号: WOS:000297347700009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64570
Appears in Collections:中国药物依赖性研究所_期刊论文

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作者单位: 1.Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA
2.Vet Affairs Connecticut Healthcare Syst, West Haven, CT USA
3.Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA
4.China Med Univ, Affiliated Hosp 1, Dept Psychiat, Shenyang, Peoples R China
5.Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA
6.Peking Univ, Natl Inst Drug Dependence, Beijing 100871, Peoples R China
7.NIMH, Gene Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA

Recommended Citation:
Zuo, Lingjun,Zhang, Clarence K.,Wang, Fei,et al. A Novel, Functional and Replicable Risk Gene Region for Alcohol Dependence Identified by Genome-Wide Association Study[J]. PLOS ONE,2011,6(11).
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