Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 55,243 bioRxiv papers from 254,840 authors.
Genome-wide association analysis links multiple psychiatric liability genes to oscillatory brain activity
Dirk J.A. Smit,
Margaret J Wright,
Jacquelyn L. Meyers,
Nicholas G Martin,
Yvonne YW Ho,
Stephen M Malone,
Scott J Burwell,
David B Chorlian,
Eco J.C. de Geus,
Narelle K. Hansell,
Catharina EM van Beijsterveldt,
Paul M Thompson,
Christopher D. Whelan,
Sarah E Medland,
William G Iacono,
Dorret I Boomsma
Posted 11 Dec 2017
bioRxiv DOI: 10.1101/232330 (published DOI: 10.1002/hbm.24238)
Posted 11 Dec 2017
Oscillatory activity is crucial for information processing in the brain, and has a long history as a biomarker for psychopathology. Variation in oscillatory activity is highly heritable, but the involvement of specific genetic variants, genes, and brain expression pathways remains elusive. Here, we present a genome-wide association study (GWAS) for the power of oscillations at standard frequencies (~2 Hz delta, ~6 Hz theta, ~10 Hz alpha, and ~20 Hz beta) of the electroencephalogram (EEG), followed up with gene-based and brain-expression analyses based on the extraction of RNA expression quantitative trait loci (eQTL) and imputation of gene expression in brain tissues by machine learning (Metaxcan). Five cohorts with eyes-closed resting EEG and genome-wide single nucleotide polymorphism (SNP) were included with data for 8425 participants. GWAS revealed a significant SNP for alpha oscillation power intronic to protein-coding gene PRKG2. PRKG2 is amongst the genes deleted in the 4q21 microdeletion syndrome which results in speech and mental retardation. GABRA2 -- a known genetic marker for alcohol use disorder and epilepsy -- significantly affected beta power, consistent with the relation between GABAA interneuron activity and beta oscillations, and between beta oscillations and alcohol use disorders. Twenty-four genes in region 3p21.1 -- previously linked to schizophrenia -- reached significance for alpha power, which fits well with observed aberrant oscillatory activity in schizophrenia. SNPs in this region were eQTLs for GLYCTK in hippocampal tissue, and eQTLs for GNL3 and ITIH4 in the frontal cortex. SNP-based imputation of hippocampal GABRA2 expression was significantly associated with beta oscillations and indicated associations of immune genes IL18R1 and IL1RL1 in the Hippocampus and Putamen with alpha oscillation strength. In conclusion, we successfully associated genes and genetic variants with oscillatory brain activity, some of which were previously associated with psychopathology. The results show how psychopathological liability genes affect brain functioning via cortical and subcortical brain expression.
- Downloaded 448 times
- Download rankings, all-time:
- Site-wide: 18,411 out of 55,243
- In genetics: 1,267 out of 3,191
- Year to date:
- Site-wide: 39,912 out of 55,243
- Since beginning of last month:
- Site-wide: 39,243 out of 55,243
Downloads over time
Distribution of downloads per paper, site-wide
- Top preprints of 2018
- Paper search
- Author leaderboards
- Overall metrics
- The API
- Email newsletter
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!