Single-nucleotide polymorphisms in corticotropin releasing hormone receptor 1 gene (CRHR1) are associated with quantitative trait of event-related potential and alcohol dependence.
Single-nucleotide polymorphisms in corticotropin releasing hormone receptor 1 gene (CRHR1) are associated with quantitative trait of event-related potential and alcohol dependence.
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DOI：
10.1111/j.1530-0277.2010.01173.x
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发表时间：
2010-06
期刊：
影响因子：
--
通讯作者：
Porjesz B
中科院分区：
文献类型：
--
作者：
Chen AC;Manz N;Tang Y;Rangaswamy M;Almasy L;Kuperman S;Nurnberger J Jr;O'Connor SJ;Edenberg HJ;Schuckit MA;Tischfield J;Foroud T;Bierut LJ;Rohrbaugh J;Rice JP;Goate A;Hesselbrock V;Porjesz B
内表型比诊断类别更能反映基因的近端效应，因此为寻找与复杂精神疾病有关的基因提供了更强大的策略。有强有力的证据表明事件相关电位 (ERP) 的 P3 波幅是酗酒和其他去抑制性疾病风险的内表型。最近的研究表明，促肾上腺皮质激素释放激素受体 1 (CRHR1) 在动物模型的环境应激反应和乙醇自我给药中发挥着至关重要的作用。本研究的目的是测试 CRHR1 基因中的单核苷酸多态性 (SNP) 与数量性状、奇怪范例中视觉目标信号处理过程中的 P3 振幅以及酒精依赖诊断之间的潜在关联。我们分析了酒精中毒遗传学合作研究 (COGA) 的样本，该样本包括来自 209 个家庭的 1049 名白人受试者（包括 472 名酒精依赖者）。使用定量传递不平衡检验（QTDT）和基于家族的关联检验（FBAT）来检验关联性，并应用错误发现率（FDR）来纠正多重比较。发现 P3 幅度和酒精依赖性与 CRHR1 基因中多个 SNP 之间存在显着相关性 (p < 0.05)。我们的结果表明，CRHR1 可能参与信息处理过程中 ERP 的 P3 部分的调节以及酒精中毒的脆弱性。这些发现强调了电生理学和内表型方法在精神疾病遗传研究中的实用性。
Endophenotypes reflect more proximal effects of genes than diagnostic categories, hence providing a more powerful strategy in searching for genes involved in complex psychiatric disorders. There is strong evidence suggesting the P3 amplitude of the event-related potential (ERP) as an endophenotype for the risk of alcoholism and other disinhibitory disorders. Recent studies demonstrated a crucial role of corticotropin releasing hormone receptor 1 (CRHR1) in the environmental stress response and ethanol self-administration in animal models. The aim of the present study was to test the potential associations between single-nucleotide polymorphisms (SNPs) in the CRHR1 gene and the quantitative trait, P3 amplitude during the processing of visual target signals in an oddball paradigm, as well as alcohol dependence diagnosis. We analyzed a sample from the Collaborative Study on the Genetics of Alcoholism (COGA) comprising 1049 Caucasian subjects from 209 families (including 472 alcohol-dependent individuals). Quantitative transmission disequilibrium test (QTDT) and family-based association test (FBAT) were used to test the association, and false discovery rate (FDR) was applied to correct for multiple comparisons. Significant associations (p < 0.05) were found between the P3 amplitude and alcohol dependence with multiple SNPs in the CRHR1 gene. Our results suggest that CRHR1 may be involved in modulating the P3 component of the ERP during information processing and in vulnerability to alcoholism. These findings underscore the utility of electrophysiology and the endophenotype approach in the genetic study of psychiatric disorders.
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影响因子：
9.8
作者：
Edenberg, HJ;Dick, DM;Begleiter, H
通讯作者：
Begleiter, H
DOI：
10.1097/00000374-199808000-00015
发表时间：
1998-08-01
影响因子：
3.2
作者：
Edenberg, HJ;Reynolds, J;Foroud, T
通讯作者：
Foroud, T
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
56.9
作者：
Gabriel, SB;Schaffner, SF;Altshuler, D
通讯作者：
Altshuler, D
DOI：
10.1016/s0168-5597(98)00002-1
发表时间：
1998-04-01
期刊：
EVOKED POTENTIALS-ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
影响因子：
--
作者：
Begleiter, H;Porjesz, B;Bloom, FE
通讯作者：
Bloom, FE