| Title |
A genome wide association study of fast beta EEG in families of European ancestry
|
|---|---|
| Published in |
International Journal of Psychophysiology, December 2016
|
| DOI | 10.1016/j.ijpsycho.2016.12.008 |
| Pubmed ID | |
| Authors |
Jacquelyn L. Meyers, Jian Zhang, Niklas Manz, Madhavi Rangaswamy, Chella Kamarajan, Leah Wetherill, David B. Chorlian, Sun J. Kang, Lance Bauer, Victor Hesselbrock, John Kramer, Samuel Kuperman, John I. Nurnberger, Jay Tischfield, Jen Chyong Wang, Howard J. Edenberg, Alison Goate, Tatiana Foroud, Bernice Porjesz |
| Abstract |
Differences in fast beta (20-28 Hz) 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 1,564 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<5x10(-8)). The most significant SNP was rs2252790 (p<2.6x10(-8); MAF= 0.36; β= 0.135). rs2252790 is an eQTL for ROS1 expressed most robustly in the temporal cortex (p= 1.2x10(-6)) and for DSE/TSPYL4 expressed most robustly in the hippocampus (p=7.3x10(-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. |
X Demographics
The data shown below were collected from the profiles of 5 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Netherlands | 2 | 40% |
| United Kingdom | 1 | 20% |
| Unknown | 2 | 40% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 4 | 80% |
| Scientists | 1 | 20% |
Mendeley readers
The data shown below were compiled from readership statistics for 54 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 2% |
| Unknown | 53 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Professor | 7 | 13% |
| Student > Master | 7 | 13% |
| Researcher | 5 | 9% |
| Student > Bachelor | 5 | 9% |
| Student > Doctoral Student | 3 | 6% |
| Other | 10 | 19% |
| Unknown | 17 | 31% |
| Readers by discipline | Count | As % |
|---|---|---|
| Psychology | 10 | 19% |
| Medicine and Dentistry | 5 | 9% |
| Neuroscience | 5 | 9% |
| Social Sciences | 3 | 6% |
| Biochemistry, Genetics and Molecular Biology | 3 | 6% |
| Other | 9 | 17% |
| Unknown | 19 | 35% |
Attention Score in Context
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#14,536,007
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Outputs from International Journal of Psychophysiology
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Outputs of similar age from International Journal of Psychophysiology
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