ArticleMolecular psychiatry2019
Human brain arousal in the resting state: a genome-wide association study.
Article in Molecular psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Guidelines for bioinformatics of single-cell sequencing data analysis in Alzheimer's disease: review, recommendation, implementation and application.Molecular neurodegeneration · 2022Pooled it
- A Neurophysiological Evaluation of Cognitive Load during Augmented Reality Interactions in Various Industrial Maintenance and Assembly Tasks.Sensors (Basel, Switzerland) · 2023Trial
- Effects and feasibility of hyperthermic baths in comparison to exercise as add-on treatment to usual care in depression: a randomised, controlled pilot study.BMC psychiatry · 2020Trial
- Research progress on TMEM proteins in cancer progression and chemoresistance (Review).International journal of molecular medicine · 2025Review
- Genome-wide analysis of brain age identifies 59 associated loci and unveils relationships with mental and physical health.Nature aging · 2025Article
- Genome data based deep learning identified new genes predicting pharmacological treatment response of attention deficit hyperactivity disorder.Translational psychiatry · 2025Article
- Multimodal state-dependent connectivity analysis of arousal and autonomic centers in the brainstem and basal forebrain.Imaging neuroscience (Cambridge, Mass.) · 2025Article
- Arousal effects on oscillatory dynamics in the non-human primate brain.Cerebral cortex (New York, N.Y. : 1991) · 2024Article
- Cohort Profile: The LIFE-Adult-Study.International journal of epidemiology · 2023Article
- Genome-Wide Association of New-Onset Hypertension According to Renin Concentration: The Korean Genome and Epidemiology Cohort Study.Journal of cardiovascular development and disease · 2022Article
- Twin studies to GWAS: there and back again.Trends in cognitive sciences · 2021Review
- The Big Five Personality Traits and Brain Arousal in the Resting State.Brain sciences · 2021Article
- Generalized and social anxiety disorder interactomes show distinctive overlaps with striosome and matrix interactomes.Scientific reports · 2021Article
- Article
- Fatigue and brain arousal in patients with major depressive disorder.European archives of psychiatry and clinical neuroscience · 2021Article
- Cell-Type-Specific Gene Modules Related to the Regional Homogeneity of Spontaneous Brain Activity and Their Associations With Common Brain Disorders.Frontiers in neuroscience · 2021Article
- Enhanced Vigilance Stability during Daytime in Insomnia Disorder.Brain sciences · 2020Article
- Fatigue in Cancer and Neuroinflammatory and Autoimmune Disease: CNS Arousal Matters.Brain sciences · 2020Article
- Vigilance Effects in Resting-State fMRI.Frontiers in neuroscience · 2020Review
- Vulnerability to bipolar disorder is linked to sleep and sleepiness.Translational psychiatry · 2019Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 ≤ p ≤ 0.011). More specifically, variants associated with high arousal levels have previously been linked to an increased risk for MDD. In line with this, the MetaXcan database suggests increased expression levels of TMEM159 in MDD, as well as Autism Spectrum Disorder, and Alzheimer's Disease. Furthermore, our pathway analyses provided evidence for a role of sodium/calcium exchangers in resting state arousal. In conclusion, the present GWAS identifies TMEM159 as a novel candidate gene which may modulate the risk for psychiatric disorders through arousal mechanisms. Our results also encourage the elaboration of the previously reported interrelations between ion-channel modulators, sleep-wake behavior, and psychiatric disorders.
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