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全基因组关联分析鉴定出影响人类脑电图的候选基因。

Genome-wide association identifies candidate genes that influence the human electroencephalogram.

机构信息

Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20852, USA.

出版信息

Proc Natl Acad Sci U S A. 2010 May 11;107(19):8695-700. doi: 10.1073/pnas.0908134107. Epub 2010 Apr 26.

Abstract

Complex psychiatric disorders are resistant to whole-genome analysis due to genetic and etiological heterogeneity. Variation in resting electroencephalogram (EEG) is associated with common, complex psychiatric diseases including alcoholism, schizophrenia, and anxiety disorders, although not diagnostic for any of them. EEG traits for an individual are stable, variable between individuals, and moderately to highly heritable. Such intermediate phenotypes appear to be closer to underlying molecular processes than are clinical symptoms, and represent an alternative approach for the identification of genetic variation that underlies complex psychiatric disorders. We performed a whole-genome association study on alpha (alpha), beta (beta), and theta (theta) EEG power in a Native American cohort of 322 individuals to take advantage of the genetic and environmental homogeneity of this population isolate. We identified three genes (SGIP1, ST6GALNAC3, and UGDH) with nominal association to variability of theta or alpha power. SGIP1 was estimated to account for 8.8% of variance in power, and this association was replicated in US Caucasians, where it accounted for 3.5% of the variance. Bayesian analysis of prior probability of association based upon earlier linkage to chromosome 1 and enrichment for vesicle-related transport proteins indicates that the association of SGIP1 with theta power is genuine. We also found association of SGIP1 with alcoholism, an effect that may be mediated via the same brain mechanisms accessed by theta EEG, and which also provides validation of the use of EEG as an endophenotype for alcoholism.

摘要

复杂的精神疾病由于遗传和病因的异质性而难以进行全基因组分析。静息脑电图(EEG)的变化与包括酒精中毒、精神分裂症和焦虑症在内的常见复杂精神疾病有关,尽管它们不能作为任何一种疾病的诊断依据。个体的 EEG 特征是稳定的,个体之间是可变的,并且具有中度到高度的遗传性。这种中间表型似乎比临床症状更接近潜在的分子过程,代表了识别复杂精神疾病遗传变异的一种替代方法。我们对一个 322 人的美国原住民队列中的 alpha(alpha)、beta(beta)和 theta(theta)EEG 功率进行了全基因组关联研究,利用了该人群隔离的遗传和环境同质性。我们确定了三个基因(SGIP1、ST6GALNAC3 和 UGDH)与 theta 或 alpha 功率变异性具有名义上的关联。SGIP1 被估计可解释功率变异的 8.8%,并且这种关联在美国白种人中得到了复制,在那里它解释了 3.5%的变异。基于先前与 1 号染色体的连锁和与囊泡相关运输蛋白的富集的关联先验概率的贝叶斯分析表明,SGIP1 与 theta 功率的关联是真实的。我们还发现 SGIP1 与酒精中毒有关,这种效应可能是通过 theta EEG 所涉及的相同大脑机制介导的,这也验证了将 EEG 用作酒精中毒的内表型的用途。

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