Human brain arousal in the resting state: a genome-wide association study
Human brain arousal in the resting state: a genome-wide association study
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DOI：
10.1038/s41380-018-0052-2
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发表时间：
2019-11-01
影响因子：
11
通讯作者：
Hegerl, Ulrich
中科院分区：
文献类型：
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作者：
Jawinski, Philippe;Kirsten, Holger;Hegerl, Ulrich
唤醒影响认知、情感和行为，并与精神疾病的病因学有关。虽然环境条件大大有助于唤醒的水平，稳定的个体间的特点是公认的，并提出了遗传基础。在这里，我们调查了分子遗传学的大脑唤醒在休息状态下进行全基因组关联研究（GWAS）。我们从基于人群的LIFE-Adult队列中选择了N = 1877名参与者。参与者接受了20分钟的闭眼静息状态EEG，使用计算机化的VIGALL 2.1（Vigilance Algorithm Leipzig）进行分析。在SNP水平上，GWAS分析显示没有全基因组显著性位点（p < 5E-8），尽管有7个位点是提示性的（p <1 E-6）。最强的命中是TMEM 159的表达数量性状基因座（eQTL）（前导SNP：rs79472635，p = 5.49E-8）。重要的是，在基因水平上，GWAS分析揭示了TMEM 159的显著证据（p = 0.013，Bonferroni校正）。通过将我们的SNP定位到来自精神病学基因组学联盟的GWAS结果，我们发现TMEM 159的所有相应标记显示出与重性抑郁症（MDD; 0.006）名义上显著的关联
Arousal affects cognition, emotion, and behavior and has been implicated in the etiology of psychiatric disorders. Although environmental conditions substantially contribute to the level of arousal, stable interindividual characteristics are well-established and a genetic basis has been suggested. Here we investigated the molecular genetics of brain arousal in the resting state by conducting a genome-wide association study (GWAS). We selected N = 1877 participants from the population-based LIFE-Adult cohort. Participants underwent a 20-min eyes-closed resting state EEG, which was analyzed using the computerized VIGALL 2.1 (Vigilance Algorithm Leipzig). At the SNP-level, GWAS analyses revealed no genome-wide significant locus (p < 5E-8), although seven loci were suggestive (p < 1E-6). The strongest hit was an expression quantitative trait locus (eQTL) of TMEM159 (lead-SNP: rs79472635, p = 5.49E-8). Importantly, at the gene-level, GWAS analyses revealed significant evidence for TMEM159 (p = 0.013, Bonferroni-corrected). By mapping our SNPs to the GWAS results from the Psychiatric Genomics Consortium, we found that all corresponding markers of TMEM159 showed nominally significant associations with Major Depressive Disorder (MDD; 0.006