酒精依赖的基于基因和基于通路的全基因组关联研究（英文）

作     者：Lingjun ZUO Clarence K.ZHANG Frederick G.SAYWARD Kei-Hoi CHEUNG Kesheng WANG John H.KRYSTAL Hongyu ZHAO Xingguang LUO 

作者机构：Department of Psychiatry Yale University School of Medicine Department of Epidemiology and Public Health Yale University School of Medicine Biostatistics Resource Keck Laboratory Department of Genetics Yale University School of Medicine Center for Medical Informatics Yale University School of Medicine Cooperative Studies Program Coordinating Center VA Connecticut Healthcare System Department of Biostatistics and Epidemiology College of Public Health East Tennessee State University 

出 版 物：《上海精神医学》 (Shanghai Archives of Psychiatry)

年 卷 期：2015年第27卷第2期

页      面：111-118页

学科分类：1002[医学-临床医学] 100205[医学-精神病与精神卫生学] 10[医学] 

基　　金：supported in part by National Institute on Drug Abuse(NIDA)grants K01 DA029643 and R01DA016750 National Institute on Alcohol Abuse and Alcoholism(NIAAA)grants R21 AA021380 and R21 AA020319 the National Alliance for Research on Schizophrenia and Depression(NARSAD)Award 17616(L.Z.) ABMRF/The Foundation for Alcohol Research(L.Z.) Funding and other supports for phenotype and genotype data were provided through the National Institutes of Health(NIH)Genes,Environment and Health Initiative(GEI)(U01HG004422,U01HG004436 and U01HG004438) the GENEVA Coordinating Center(U01HG004446) the NIAAA(U10AA008401,R01AA013320,P60AA011998) the NIDA(R01DA013423) the National Cancer Institute(P01 CA089392) the NIH contract‘High throughput genotyping for studying the genetic contributions to human disease’(HHSN268200782096C) the Center for Inherited Disease Research(CIDR) the National Center for Biotechnology Information.Genotyping was performed at the Johns Hopkins University Center for Inherited Disease Research 

主　　题：全基因组 酒精 基础 关联 神经生物学 细胞外基质 信号通路 相互作用 

摘      要：背景:信号通路中风险基因的构成可能可以解释酒精依赖风险基因协同的神经生物学作用。目的:识别酒精依赖的风险基因和风险基因通路。方法:我们采用基因富集(gene-set-rich)分析方法对酒精依赖进行了基于通路的全基因组关联分析(GWAS)。在包括1409名欧裔美国人(European-American,EA)酒精依赖者和1518名EA健康对照者的探索性样本人群中检测了近一百万个基因标志物。此外,将681名非裔美国人(African-American,AA)病例和508名AA健康受试者作为重测样本。结果:我们发现了几个与酒精依赖显著相关的可重复的全基因组风险基因和风险通路。在多重比较Bonferroni校正后,细胞-细胞外基质相互作用通路(EA样本中p2.0E-4)和该通路中PXN基因(编码桩蛋白paxillin)(EA样本中p=3.9E-7)是最有可能的酒精依赖的危险因素。在EA样本(0.015≤p≤0.035)和AA样本(0.025≤p≤0.050)中还有两条富含酒精依赖相关基因的可重复的通路:Na+/Cl-依赖性神经递质转运体通路和其他聚糖降解通路。结论:一些基因和生物信号传导过程可能与酒精依赖的风险相关,本研究的发现为此提供了新的证据。