Genetic Epidemiology, Translational Neurogenomics, Psychiatric 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.
QIMR Home Page
GenEpi Home Page
About GenEpi
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
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 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.
DATE PUBLISHED
2018 11
HISTORY
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
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: 11
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
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
GRANTS
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
GENERAL NOTE
KEYWORDS
KEYWORD
Genome-Wide Association Study (GWAS)
SNP heritability
brain expression pathway
electroencephalography (EEG)
endophenotype
genetic correlation
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adolescent
Adult
Aged
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
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's