ItemArticle

A genome wide association study of fast beta EEG in families of European ancestry

Title
A genome wide association study of fast beta EEG in families of European ancestry
Creator
Meyers J.L.; Zhang J.; Manz N.; Rangaswamy M.; Kamarajan C.; Wetherill L.; Chorlian D.B.; Kang S.J.; Bauer L.; Hesselbrock V.; Kramer J.; Kuperman S.; Nurnberger J.I., Jr.; Tischfield J.; Wang J.C.; Edenberg H.J.; Goate A.; Foroud T.; Porjesz B.
Description
Background Differences in fast beta (2028Hz) 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). Method 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. Results Three intronic variants located within DSE (dermatan sulfate epimerase) on 6q22 were associated with fast beta EEG at a genome wide significant level (p<5נ10?8). The most significant SNP was rs2252790 (p<2.6נ10?8; MAF=0.36; ?=0.135). rs2252790 is an eQTL for ROS1 expressed most robustly in the temporal cortex (p=1.2נ10?6) and for DSE/TSPYL4 expressed most robustly in the hippocampus (p=7.3נ10?4; ?=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). Discussion 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. 2016 Elsevier B.V.
Source
International Journal of Psychophysiology, Vol-115, pp. 74-85.
Date
2017-01-01
Publisher
Elsevier B.V.
Subject
Electrophysiology; Endophenotype; Genome-Wide Association Study (GWAS); Resting EEG
Coverage
Meyers J.L., Henri Begleiter Neurodynamics Laboratory, Department of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, NY, United States; Zhang J., Henri Begleiter Neurodynamics Laboratory, Department of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, NY, United States; Manz N., Henri Begleiter Neurodynamics Laboratory, Department of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, NY, United States, Department of Physics, College of Wooster, Wooster, OH, United States; Rangaswamy M., Department of Psychology, Christ University, Bangalore, India; Kamarajan C., Henri Begleiter Neurodynamics Laboratory, Department of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, NY, United States; Wetherill L., Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States; Chorlian D.B., Henri Begleiter Neurodynamics Laboratory, Department of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, NY, United States; Kang S.J., Albany Stratton VA Medical Center, Albany, NY, United States; Bauer L., University of Connecticut School of Medicine, Farmington, CT, United States; Hesselbrock V., University of Connecticut School of Medicine, Farmington, CT, United States; Kramer J., Department of Psychiatry, University of Iowa, Iowa City, IA, United States; Kuperman S., Department of Psychiatry, University of Iowa, Iowa City, IA, United States; Nurnberger J.I., Jr., Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States; Tischfield J., Rutgers University, Piscataway, NJ, United States; Wang J.C., Icahn School of Medicine at Mt. Sinai, New York, NY, United States; Edenberg H.J., Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, United States; Goate A., Icahn School of Medicine at Mt. Sinai, New York, NY, United States; Foroud T., Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States; Porjesz B., Henri Begleiter Neurodynamics Laboratory, Department of Psychiatry and Behavioral Sciences, SUNY Downstate Medical Center, Brooklyn, NY, United States
Rights
All Open Access; Green Open Access
Relation
ISSN: 1678760; PubMed ID: 28040410; CODEN: IJPSE
Format
Online
Language
English
Type
Article

Collection

Articles

Citation

Meyers J.L.; Zhang J.; Manz N.; Rangaswamy M.; Kamarajan C.; Wetherill L.; Chorlian D.B.; Kang S.J.; Bauer L.; Hesselbrock V.; Kramer J.; Kuperman S.; Nurnberger J.I., Jr.; Tischfield J.; Wang J.C.; Edenberg H.J.; Goate A.; Foroud T.; Porjesz B., “A genome wide association study of fast beta EEG in families of European ancestry,” CHRIST (Deemed To Be University) Institutional Repository, accessed February 23, 2025, https://archives.christuniversity.in/items/show/17102.

Output Formats