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PMID |
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TITLE |
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Genome-wide association analysis links multiple psychiatric liability genes to oscillatory brain activity. |
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ABSTRACT |
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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 current understanding of specific genetic influences remains limited. We performed the largest genome-wide association study to date of oscillatory power during eyes-closed resting electroencephalogram (EEG) across a range of frequencies (delta 1-3.75 Hz, theta 4-7.75 Hz, alpha 8-12.75 Hz, and beta 13-30 Hz) in 8,425 subjects. Additionally, we performed KGG positional gene-based analysis and brain-expression analyses. GABRA2-a known genetic marker for alcohol use disorder and epilepsy-significantly affected beta power, consistent with the known relation between GABAA interneuron activity and beta oscillations. Tissue-specific SNP-based imputation of gene-expression levels based on the GTEx database revealed that hippocampal GABRA2 expression may mediate this effect. Twenty-four genes at 3p21.1 were significant for alpha power (FDR q < .05). SNPs in this region were linked to expression of GLYCTK in hippocampal tissue, and GNL3 and ITIH4 in the frontal cortex-genes that were previously implicated in schizophrenia and bipolar disorder. In sum, we identified several novel genetic variants associated with oscillatory brain activity; furthermore, we replicated and advanced understanding of previously known genes associated with psychopathology (i.e., schizophrenia and alcohol use disorders). Importantly, these psychopathological liability genes affect brain functioning, linking the genes' expression to specific cortical/subcortical brain regions. |
© 2018 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. |
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DATE PUBLISHED |
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HISTORY |
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PUBSTATUS |
PUBSTATUSDATE |
received |
2017/12/18 |
revised |
2018/04/26 |
accepted |
2018/05/21 |
pubmed |
2018/06/28 06:00 |
medline |
2019/06/14 06:00 |
entrez |
2018/06/28 06:00 |
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AUTHORS |
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NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
Smit DJA |
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Smit |
Dirk J A |
DJA |
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Psychiatry department, Amsterdam Neuroscience, Academic Medical Center, University of Amsterdam, The Netherlands. |
Wright MJ |
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Wright |
Margaret J |
MJ |
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Centre of Advanced Imaging, University Queensland, Brisbane, Australia. |
Meyers JL |
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Meyers |
Jacquelyn L |
JL |
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Henri Begleiter Neurodynamics Lab., Department of Psychiatry, State University of New York Downstate Medical Center, Brooklyn, New York. |
Martin NG |
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Martin |
Nicholas G |
NG |
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QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
Ho YYW |
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Ho |
Yvonne Y W |
YYW |
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QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
Malone SM |
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Malone |
Stephen M |
SM |
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Department of Psychology, University of Minnesota, Minneapolis, Minnesota. |
Zhang J |
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Zhang |
Jian |
J |
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Henri Begleiter Neurodynamics Lab., Department of Psychiatry, State University of New York Downstate Medical Center, Brooklyn, New York. |
Burwell SJ |
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Burwell |
Scott J |
SJ |
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Department of Psychology, University of Minnesota, Minneapolis, Minnesota. |
Chorlian DB |
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Chorlian |
David B |
DB |
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Henri Begleiter Neurodynamics Lab., Department of Psychiatry, State University of New York Downstate Medical Center, Brooklyn, New York. |
de Geus EJC |
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de Geus |
Eco J C |
EJC |
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Biological Psychology, Amsterdam Public Health research institute, Vrije Universiteit Amsterdam, The Netherlands. |
Denys D |
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Denys |
Damiaan |
D |
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Psychiatry department, Amsterdam Neuroscience, Academic Medical Center, University of Amsterdam, The Netherlands. |
Hansell NK |
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Hansell |
Narelle K |
NK |
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Queensland Brain Institute, University of Queensland, Brisbane, Australia. |
Hottenga JJ |
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Hottenga |
Jouke-Jan |
JJ |
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Biological Psychology, Amsterdam Public Health research institute, Vrije Universiteit Amsterdam, The Netherlands. |
McGue M |
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McGue |
Matt |
M |
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Department of Psychology, University of Minnesota, Minneapolis, Minnesota. |
van Beijsterveldt CEM |
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van Beijsterveldt |
Catharina E M |
CEM |
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Biological Psychology, Amsterdam Public Health research institute, Vrije Universiteit Amsterdam, The Netherlands. |
Jahanshad N |
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Jahanshad |
Neda |
N |
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Imaging Genetics Center, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of University of Southern California, Marina del Rey, California. |
Thompson PM |
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Thompson |
Paul M |
PM |
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Imaging Genetics Center, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of University of Southern California, Marina del Rey, California. |
Whelan CD |
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Whelan |
Christopher D |
CD |
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Imaging Genetics Center, USC Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of University of Southern California, Marina del Rey, California. |
Medland SE |
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Medland |
Sarah E |
SE |
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QIMR Berghofer Medical Research Institute, Brisbane, Australia. |
Porjesz B |
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Porjesz |
Bernice |
B |
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Henri Begleiter Neurodynamics Lab., Department of Psychiatry, State University of New York Downstate Medical Center, Brooklyn, New York. |
Lacono WG |
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Lacono |
William G |
WG |
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Department of Psychology, University of Minnesota, Minneapolis, Minnesota. |
Boomsma DI |
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Boomsma |
Dorret I |
DI |
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Biological Psychology, Amsterdam Public Health research institute, Vrije Universiteit Amsterdam, The Netherlands. |
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INVESTIGATORS |
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JOURNAL |
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VOLUME: 39 |
ISSUE: 11 |
TITLE: Human brain mapping |
ISOABBREVIATION: Hum Brain Mapp |
YEAR: 2018 |
MONTH: 11 |
DAY: |
MEDLINEDATE: |
SEASON: |
CITEDMEDIUM: Internet |
ISSN: 1097-0193 |
ISSNTYPE: Electronic |
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MEDLINE JOURNAL |
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MEDLINETA: Hum Brain Mapp |
COUNTRY: United States |
ISSNLINKING: 1065-9471 |
NLMUNIQUEID: 9419065 |
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PUBLICATION TYPE |
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PUBLICATIONTYPE TEXT |
Journal Article |
Research Support, N.I.H., Extramural |
Research Support, Non-U.S. Gov't |
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COMMENTS AND CORRECTIONS |
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GRANTS |
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GRANTID |
AGENCY |
COUNTRY |
R37 AA009367 |
NIAAA NIH HHS |
United States |
U01 HG004438 |
NHGRI NIH HHS |
United States |
R01 MH081802 |
NIMH NIH HHS |
United States |
R01 AA009367 |
NIAAA NIH HHS |
United States |
RC2 MH089995 |
NIMH NIH HHS |
United States |
U01 DA024417 |
NIDA NIH HHS |
United States |
R01 DA024417 |
NIDA NIH HHS |
United States |
U24 MH068457 |
NIMH NIH HHS |
United States |
HHSN268200782096C |
NHLBI NIH HHS |
United States |
R01 DK092127 |
NIDDK NIH HHS |
United States |
U10 AA008401 |
NIAAA NIH HHS |
United States |
R37 DA005147 |
NIDA NIH HHS |
United States |
U01 MH109528 |
NIMH NIH HHS |
United States |
R01 DA013240 |
NIDA NIH HHS |
United States |
RC2 MH089951 |
NIMH NIH HHS |
United States |
R01 DA005147 |
NIDA NIH HHS |
United States |
R01 DA036216 |
NIDA NIH HHS |
United States |
R01 HD042157 |
NICHD NIH HHS |
United States |
K01 DA037914 |
NIDA NIH HHS |
United States |
HHSN268200782096C |
NHGRI NIH HHS |
United States |
U54 EB020403 |
NIBIB NIH HHS |
United States |
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GENERAL NOTE |
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KEYWORDS |
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KEYWORD |
Genome-Wide Association Study (GWAS) |
SNP heritability |
brain expression pathway |
electroencephalography (EEG) |
endophenotype |
genetic correlation |
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MESH HEADINGS |
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DESCRIPTORNAME |
QUALIFIERNAME |
Adolescent |
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Adult |
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Aged |
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Brain |
physiopathology |
Child |
physiopathology |
Child, Preschool |
physiopathology |
Cohort Studies |
physiopathology |
Electroencephalography |
physiopathology |
Female |
physiopathology |
Gene Expression |
physiopathology |
Genetic Predisposition to Disease |
physiopathology |
Genome-Wide Association Study |
physiopathology |
Humans |
physiopathology |
Male |
physiopathology |
Mental Disorders |
metabolism |
Middle Aged |
metabolism |
Periodicity |
metabolism |
Polymorphism, Single Nucleotide |
metabolism |
Rest |
metabolism |
Young Adult |
metabolism |
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SUPPLEMENTARY MESH |
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GENE SYMBOLS |
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CHEMICALS |
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OTHER ID's |
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