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Genome‐wide association analysis links multiple psychiatric liability genes to oscillatory brain activity
- Source :
- Human Brain Mapping, Human brain mapping, 39(11), 4183-4195. Wiley-Liss Inc., Human Brain Mapping, 39(11), 4183-4195. Wiley-Liss Inc., Smit, D J A, Wright, M J, Meyers, J L, Martin, N G, Ho, Y Y W, Malone, S M, Zhang, J, Burwell, S J, Chorlian, D B, de Geus, E J C, Denys, D, Hansell, N K, Hottenga, J J, McGue, M, van Beijsterveldt, C E M, Jahanshad, N, Thompson, P M, Whelan, C D, Medland, S E, Porjesz, B, Lacono, W G & Boomsma, D I 2018, ' Genome-wide association analysis links multiple psychiatric liability genes to oscillatory brain activity ', Human Brain Mapping, vol. 39, no. 11, pp. 4183-4195 . https://doi.org/10.1002/hbm.24238
- Publication Year :
- 2018
- Publisher :
- John Wiley and Sons Inc., 2018.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Netherlands Twin Register (NTR)
Male
Periodicity
brain expression pathway
Brain activity and meditation
Gene Expression
Genome-wide association study
Electroencephalography
Hippocampal formation
Cohort Studies
0302 clinical medicine
electroencephalography (EEG)
Child
Research Articles
Genetics
0303 health sciences
Radiological and Ultrasound Technology
biology
medicine.diagnostic_test
Mental Disorders
Brain
Middle Aged
genetic correlation
endophenotype
Neurology
Child, Preschool
Female
Anatomy
Research Article
Adult
Adolescent
Rest
Single-nucleotide polymorphism
Quantitative trait locus
Genome‐Wide Association Study (GWAS)
Polymorphism, Single Nucleotide
SNP heritability
03 medical and health sciences
Young Adult
SDG 3 - Good Health and Well-being
medicine
SNP
Humans
Radiology, Nuclear Medicine and imaging
GABRA2
Genetic Predisposition to Disease
Bipolar disorder
030304 developmental biology
Aged
Genome-Wide Association Study (GWAS)
medicine.disease
030104 developmental biology
Endophenotype
Expression quantitative trait loci
biology.protein
Neurology (clinical)
Neuroscience
Imputation (genetics)
030217 neurology & neurosurgery
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 10970193 and 10659471
- Volume :
- 39
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Human Brain Mapping
- Accession number :
- edsair.doi.dedup.....f04e6f31d1b64c060fc20d67e8c45509