IR@PKUHSC  > 中国药物依赖性研究所
学科主题药物依赖
A Novel, Functional and Replicable Risk Gene Region for Alcohol Dependence Identified by Genome-Wide Association Study
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
2011-11-07
DOI10.1371/journal.pone.0026726
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
WOS记录号WOS:000297347700009
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
资助机构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
引用统计
被引频次:35[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/400002259/64570
专题中国药物依赖性研究所
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
推荐引用方式
GB/T 7714
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).
APA Zuo, Lingjun.,Zhang, Clarence K..,Wang, Fei.,Li, Chiang-Shan R..,Zhao, Hongyu.,...&Luo, Xingguang.(2011).A Novel, Functional and Replicable Risk Gene Region for Alcohol Dependence Identified by Genome-Wide Association Study.PLOS ONE,6(11).
MLA Zuo, Lingjun,et al."A Novel, Functional and Replicable Risk Gene Region for Alcohol Dependence Identified by Genome-Wide Association Study".PLOS ONE 6.11(2011).
条目包含的文件
条目无相关文件。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Zuo, Lingjun]的文章
[Zhang, Clarence K.]的文章
[Wang, Fei]的文章
百度学术
百度学术中相似的文章
[Zuo, Lingjun]的文章
[Zhang, Clarence K.]的文章
[Wang, Fei]的文章
必应学术
必应学术中相似的文章
[Zuo, Lingjun]的文章
[Zhang, Clarence K.]的文章
[Wang, Fei]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。