Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
29947131
TITLE
Genome-wide association analysis links multiple psychiatric liability genes to oscillatory brain activity.
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 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 GABA 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.
DATE PUBLISHED
2018 Nov
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2017/12/18
revised 2018/04/26
accepted 2018/05/21
pubmed 2018/06/28 06:00
medline 2018/06/28 06:00
entrez 2018/06/28 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Smit DJA Smit Dirk J A DJA Psychiatry department, Amsterdam Neuroscience, Academic Medical Center, University of Amsterdam, The Netherlands.
Wright MJ Wright Margaret J MJ Centre of Advanced Imaging, University Queensland, Brisbane, Australia.
Meyers JL Meyers Jacquelyn L JL Henri Begleiter Neurodynamics Lab., Department of Psychiatry, State University of New York Downstate Medical Center, Brooklyn, New York.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Ho YYW Ho Yvonne Y W YYW QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Malone SM Malone Stephen M SM Department of Psychology, University of Minnesota, Minneapolis, Minnesota.
Zhang J Zhang Jian J Henri Begleiter Neurodynamics Lab., Department of Psychiatry, State University of New York Downstate Medical Center, Brooklyn, New York.
Burwell SJ Burwell Scott J SJ Department of Psychology, University of Minnesota, Minneapolis, Minnesota.
Chorlian DB Chorlian David B DB Henri Begleiter Neurodynamics Lab., Department of Psychiatry, State University of New York Downstate Medical Center, Brooklyn, New York.
de Geus EJC de Geus Eco J C EJC Biological Psychology, Amsterdam Public Health research institute, Vrije Universiteit Amsterdam, The Netherlands.
Denys D Denys Damiaan D Psychiatry department, Amsterdam Neuroscience, Academic Medical Center, University of Amsterdam, The Netherlands.
Hansell NK Hansell Narelle K NK Queensland Brain Institute, University of Queensland, Brisbane, Australia.
Hottenga JJ Hottenga Jouke-Jan JJ Biological Psychology, Amsterdam Public Health research institute, Vrije Universiteit Amsterdam, The Netherlands.
McGue M McGue Matt M Department of Psychology, University of Minnesota, Minneapolis, Minnesota.
van Beijsterveldt CEM van Beijsterveldt Catharina E M CEM Biological Psychology, Amsterdam Public Health research institute, Vrije Universiteit Amsterdam, The Netherlands.
Jahanshad N Jahanshad Neda N 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 Thompson Paul M PM 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 Whelan Christopher D CD 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 Medland Sarah E SE QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Porjesz B Porjesz Bernice B Henri Begleiter Neurodynamics Lab., Department of Psychiatry, State University of New York Downstate Medical Center, Brooklyn, New York.
Lacono WG Lacono William G WG Department of Psychology, University of Minnesota, Minneapolis, Minnesota.
Boomsma DI Boomsma Dorret I DI Biological Psychology, Amsterdam Public Health research institute, Vrije Universiteit Amsterdam, The Netherlands.
INVESTIGATORS
JOURNAL
VOLUME: 39
ISSUE: 11
TITLE: Human brain mapping
ISOABBREVIATION: Hum Brain Mapp
YEAR: 2018
MONTH: Nov
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1097-0193
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Hum Brain Mapp
COUNTRY: United States
ISSNLINKING: 1065-9471
NLMUNIQUEID: 9419065
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
RC2 MH089951 NIMH NIH HHS United States
HHSN268200782096C COGA
R01 DA005147 NIDA NIH HHS United States
MH081802 NIH R01D0042157-01A
R01 DA036216 NIDA NIH HHS United States
480-04-004 Vrije Universiteit
451-04-034 Vrije Universiteit
DA 024417 National Institutes of Health (NIH)
R37 AA009367 NIAAA NIH HHS United States
VU-USF 96/22 BBR Foundation (NARSAD)
NIH GEI U01HG004438 COGA
1RC2 MH089995 Grand Opportunity grants
U01 HG004438 NHGRI NIH HHS United States
21668 BBR Foundation (NARSAD)
R01 MH081802 NIMH NIH HHS United States
Addiction-31160008 Vrije Universiteit
ERC FP7/2007-2013
1RC2 MH089951 Grand Opportunity grants
R01 AA009367 NIAAA NIH HHS United States
DA 05147 National Institutes of Health (NIH)
RC2 MH089995 NIMH NIH HHS United States
904-61-193 Vrije Universiteit
A79801419 Australian Research Council
NHMRC 389891 Australian Research Council
A79600334 Australian Research Council
HFSP RG0154/1998-B BBR Foundation (NARSAD)
NIH NIAAA U10AA00840 COGA
KNAW PAH/6635 BBR Foundation (NARSAD)
R01 HD042157 NICHD NIH HHS United States
K01 DA037914 NIDA NIH HHS United States
184.021.007 Vrije Universiteit
NWO/MagW VENI-451-08-026
985-10-002 Vrije Universiteit
463-06-001 Vrije Universiteit
U01 DA024417 NIDA NIH HHS United States
NOW/ZonMW 904-61-090 Vrije Universiteit
ERC-230374
HHSN268200782096C NHGRI NIH HHS United States
ERC Advanced 230374
U54 EB020403 NIBIB NIH HHS United States
R01 DA024417 NIDA NIH HHS United States
Starting 284167
BBMRI-NL Vrije Universiteit
NIH K01DA037914 Fellowship
NWO 911-09- 032
400-05-717 Vrije Universiteit
NIMH U24 MH068457-06
Middelgroot-911-09-032 Vrije Universiteit
Spinozapremie 56-464-14192 Vrije Universiteit
912-10-020 Vrije Universiteit
U24 MH068457 NIMH NIH HHS United States
DA 36216 National Institutes of Health (NIH)
R01 DK092127-04 NIH R01D0042157-01A
HHSN268200782096C NHLBI NIH HHS United States
NWO-Groot 480-15-001/674 Vrije Universiteit
NWO/SPI 56-464-14192
A79906588 Australian Research Council
NWO 480-04- 004
DP0212016 Australian Research Council
R01 DK092127 NIDDK NIH HHS United States
U10 AA008401 NIAAA NIH HHS United States
R37 DA005147 NIDA NIH HHS United States
APP1103623 Fellowship
ENGAGE HEALTH-F4-2007-201413
R01 DA013240 NIDA NIH HHS United States
GENERAL NOTE
KEYWORDS
KEYWORD
Genome-Wide Association Study (GWAS)
SNP heritability
brain expression pathway
electroencephalography (EEG)
endophenotype
genetic correlation
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's