Genome-wide association study of theta band event-related oscillations identifies serotonin receptor gene HTR7 influencing risk of alcohol dependence.
Genome-wide association study of theta band event-related oscillations identifies serotonin receptor gene HTR7 influencing risk of alcohol dependence.
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DOI：
10.1002/ajmg.b.31136
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发表时间：
2011-01
影响因子：
2.8
通讯作者：
Almasy, Laura
中科院分区：
文献类型：
--
作者：
Zlojutro, Mark;Manz, Niklas;Rangaswamy, Madhavi;Xuei, Xiaoling;Flury-Wetherill, Leah;Koller, Daniel;Bierut, Laura J.;Goate, Alison;Hesselbrock, Victor;Kuperman, Samuel;Nurnberger, John, Jr.;Rice, John P.;Schuckit, Marc A.;Foroud, Tatiana;Edenberg, Howard J.;Porjesz, Bernice;Almasy, Laura
关键词：
事件相关脑振荡（EROs）代表了人类感知和认知表现的高度遗传性神经电相关，在各种精神疾病患者中表现出明显的缺陷。我们报告了第一个全基因组关联研究（GWAS）的结果，该研究是由1064名来自酒精依赖研究的非相关个体在P300反应期间由视觉奇球靶点引起的ERO内表型-额叶θ ERO。从theta ERO GWAS中选择42个Illumina HumanHap 1M微阵列的snp用于基于家族的样本（N = 1,095）的复制，其中4个标记显示名义上显著的关联。两阶段研究中最显著的标记是位于染色体2q11上的ARID蛋白5A基因（ARID5A）内的rs4907240（未经调整，Fisher’s combined P = 3.68 × 10−6）。然而，最有趣的关联是与染色体10q23上5 -羟色胺受体基因HTR7上的rs7916403有关（组合P = 1.53 × 10−4），暗示5 -羟色胺能系统在theta EROs的神经生理基础中起作用。此外，我们还测试了有希望的snp与酒精依赖诊断的关联（DSM-IV），揭示了GWAS病例对照中HTR7多态性与HTR7多态性的显著关系（P = 0.008）。在病例对照和基于家庭的样本中，酒精依赖也检测到显著的隐性遗传效应（P分别= 0.031和0.042），纯合子中HTR7风险等位基因对应于theta ERO减少。这些结果表明血清素能系统在酒精依赖的生物学基础中的作用，并强调了分析大脑振荡作为理解复杂遗传精神疾病的有力方法的实用性。
Event-related brain oscillations (EROs) represent highly heritable neuroelectrical correlates of human perception and cognitive performance that exhibit marked deficits in patients with various psychiatric disorders. We report the results of the first genome-wide association study (GWAS) of an ERO endophenotype – frontal theta ERO evoked by visual oddball targets during P300 response in 1,064 unrelated individuals drawn from a study of alcohol dependence. Forty-two SNPs of the Illumina HumanHap 1M microarray were selected from the theta ERO GWAS for replication in family-based samples (N = 1,095), with four markers revealing nominally significant association. The most significant marker from the two-stage study is rs4907240 located within ARID protein 5A gene (ARID5A) on chromosome 2q11 (unadjusted, Fisher’s combined P = 3.68 × 10−6). However, the most intriguing association to emerge is with rs7916403 in serotonin receptor gene HTR7 on chromosome 10q23 (combined P = 1.53 × 10−4), implicating the serotonergic system in the neurophysiological underpinnings of theta EROs. Moreover, promising SNPs were tested for association with diagnoses of alcohol dependence (DSM-IV), revealing a significant relationship with the HTR7 polymorphism among GWAS case-controls (P = 0.008). Significant recessive genetic effects were also detected for alcohol dependence in both case-control and family-based samples (P = 0.031 and 0.042, respectively), with the HTR7 risk allele corresponding to theta ERO reductions among homozygotes. These results suggest a role of the serotonergic system in the biological basis of alcohol dependence and underscore the utility of analyzing brain oscillations as a powerful approach to understanding complex genetic psychiatric disorders.
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影响因子：
3
作者：
Basar, E;Basar-Eroglu, C;Schürmann, M
通讯作者：
Schürmann, M
影响因子：
30.8
作者：
de Bakker, PIW;Yelensky, R;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
6
作者：
Dick, Danielle M.;Agrawal, Arpana;Bierut, Laura J.
通讯作者：
Bierut, Laura J.
影响因子：
9.8
作者：
Edenberg, HJ;Dick, DM;Begleiter, H
通讯作者：
Begleiter, H
影响因子：
4.2
作者：
Agrawal, Arpana;Hinrichs, Anthony L.;Bierut, Laura J.
通讯作者：
Bierut, Laura J.