Human brain arousal in the resting state: a genome-wide association study
Philippe Jawinski, Holger Kirsten, Christian Sander, Janek Spada, Christine Ulke, Jue Huang, Ralph Burkhardt, Markus Scholz et al.. Molecular psychiatry, 2018-04-27
Topic: Genetics and APOE
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.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Jawinski, P., Kirsten, H., Sander, C., Spada, J., Ulke, C., Huang, J., et al. (2019). Human brain arousal in the resting state: a genome-wide association study. Molecular psychiatry. https://doi.org/10.1038/s41380-018-0052-2
Vancouver
Jawinski P, Kirsten H, Sander C, Spada J, Ulke C, Huang J, et al. Human brain arousal in the resting state: a genome-wide association study. Molecular psychiatry. 2019. doi:10.1038/s41380-018-0052-2. PMID: 29703947.
BibTeX
@article{jawinski2019-29703947,
author = {Jawinski, Philippe and Kirsten, Holger and Sander, Christian and Spada, Janek and Ulke, Christine and Huang, Jue and Burkhardt, Ralph and Scholz, Markus and others},
title = {{Human brain arousal in the resting state: a genome-wide association study}},
journal = {Molecular psychiatry},
year = {2019},
doi = {10.1038/s41380-018-0052-2},
pmid = {29703947},
url = {https://doi.org/10.1038/s41380-018-0052-2}
}
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Key findings
- At the SNP-level, GWAS analyses revealed no genome-wide significant locus (p < 5E-8), although seven loci were suggestive (p < 1E-6).
- 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 conclusion, the present GWAS identifies TMEM159 as a novel candidate gene which may modulate the risk for psychiatric disorders through arousal mechanisms.
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Study details
- Participants1,877
- Evidence strengthModerate
How this study scored 57/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 32 of the 56 points we could judge it on, which is 57 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Molecular psychiatry) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,877 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29703947) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 32 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 32 of the 56 points we could judge it on is 57 out of 100. |
| Total | 57 / 100 | — |
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