Journal article
A genome wide association study of fast beta EEG in families of European ancestry
International journal of psychophysiology, Vol.115, pp.74-85
05/2017
DOI: 10.1016/j.ijpsycho.2016.12.008
PMCID: PMC5426060
PMID: 28040410
Abstract
Differences in fast beta (20–28Hz) electroencephalogram (EEG) oscillatory activity distinguish some individuals with psychiatric and substance use disorders, suggesting that it may be a useful endophenotype for studying the genetics of disorders characterized by neural hyper-excitability. Despite the high heritability estimates provided by twin and family studies, there have been relatively few genetic studies of beta EEG, and to date only one genetic association finding has replicated (i.e., GABRA2).
In a sample of 1564 individuals from 117 families of European Ancestry (EA) drawn from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed a Genome-Wide Association Study (GWAS) on resting-state fronto-central fast beta EEG power, adjusting regression models for family relatedness, age, sex, and ancestry. To further characterize genetic findings, we examined the functional and behavioral significance of GWAS findings.
Three intronic variants located within DSE (dermatan sulfate epimerase) on 6q22 were associated with fast beta EEG at a genome wide significant level (p<5×10−8). The most significant SNP was rs2252790 (p<2.6×10−8; MAF=0.36; β=0.135). rs2252790 is an eQTL for ROS1 expressed most robustly in the temporal cortex (p=1.2×10−6) and for DSE/TSPYL4 expressed most robustly in the hippocampus (p=7.3×10−4; β=0.29). Previous studies have indicated that DSE is involved in a network of genes integral to membrane organization; gene-based tests indicated that several variants within this network (i.e., DSE, ZEB2, RND3, MCTP1, and CTBP2) were also associated with beta EEG (empirical p<0.05), and of these genes, ZEB2 and CTBP2 were associated with DSM-V Alcohol Use Disorder (AUD; empirical p<0.05).'
In this sample of EA families enriched for AUDs, fast beta EEG is associated with variants within DSE on 6q22; the most significant SNP influences the mRNA expression of DSE and ROS1 in hippocampus and temporal cortex, brain regions important for beta EEG activity. Gene-based tests suggest evidence of association with related genes, ZEB2, RND3, MCTP1, CTBP2, and beta EEG. Converging data from GWAS, gene expression, and gene-networks presented in this study provide support for the role of genetic variants within DSE and related genes in neural hyperexcitability, and has highlighted two potential candidate genes for AUD and/or related neurological conditions: ZEB2 and CTBP2. However, results must be replicated in large, independent samples.
•GWAS of resting state fast beta (20–28Hz) EEG (F3-C3) in COGA families of European Ancestry.•Fast beta EEG is genome-wide associated with three variants within DSE (6q22).•rs2252790 influences mRNA expression in brain tissue.•Related genes ZEB2, RND3, MCTP1, and CTBP2 are associated with beta EEG.
Details
- Title: Subtitle
- A genome wide association study of fast beta EEG in families of European ancestry
- Creators
- Jacquelyn L. Meyers - SUNY Downstate Medical CenterJian Zhang - SUNY Downstate Medical CenterNiklas Manz - SUNY Downstate Medical CenterMadhavi Rangaswamy - Christ UniversityChella Kamarajan - SUNY Downstate Medical CenterLeah Wetherill - Indiana UniversityDavid B. Chorlian - SUNY Downstate Medical CenterSun J. Kang - Albany Stratton VA Medical Center AlbanyLance Bauer - University of ConnecticutVictor Hesselbrock - University of ConnecticutJohn Kramer - University of IowaSamuel Kuperman - University of IowaJohn I. Nurnberger - Indiana UniversityJay Tischfield - Rutgers, The State University of New JerseyJen Chyong Wang - Icahn School of Medicine at Mount SinaiHoward J. Edenberg - Indiana UniversityAlison Goate - Icahn School of Medicine at Mount SinaiTatiana Foroud - Indiana UniversityBernice Porjesz - SUNY Downstate Medical Center
- Resource Type
- Journal article
- Publication Details
- International journal of psychophysiology, Vol.115, pp.74-85
- Publisher
- Elsevier B.V
- DOI
- 10.1016/j.ijpsycho.2016.12.008
- PMID
- 28040410
- PMCID
- PMC5426060
- ISSN
- 0167-8760
- eISSN
- 1872-7697
- Grant note
- name: NIDA, award: K01DA037914; DOI: 10.13039/100000002, name: NIH, award: U10AA008401; name: NCI Cancer Center, award: P30 CA91842; name: ICTS/CTSA, award: UL1RR024992
- Language
- English
- Date published
- 05/2017
- Academic Unit
- Psychiatry
- Record Identifier
- 9984293656502771
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