An endophenotype approach to the genetics of alcohol dependence: a genome wide association study of fast beta EEG in families of African ancestry.
- Authors
- Meyers, J L; Zhang, J; Wang, J C; Su, J; Kuo, S I; Kapoor, M; Wetherill, L; Bertelsen, S; Lai, D; Salvatore, J E; Kamarajan, C; Chorlian, D; Agrawal, A; Almasy, L; Bauer, L; Bucholz, K K; Chan, G; Hesselbrock, V; Koganti, L; Kramer, J; Kuperman, S; Manz, N; Pandey, A; Seay, M; Scott, D; Taylor, R E; Dick, D M; Edenberg, H J; Goate, A; Foroud, T; Porjesz, B
- Year
- 2017
- Journal
- Molecular psychiatry
- PMID
- 28070124
- DOI
- 10.1038/mp.2016.239
- PMCID
- PMC5503794
Fast beta (20-28 Hz) electroencephalogram (EEG) oscillatory activity may be a useful endophenotype for studying the genetics of disorders characterized by neural hyperexcitability, including substance use disorders (SUDs). However, the genetic underpinnings of fast beta EEG have not previously been studied in a population of African-American ancestry (AA). In a sample of 2382 AA individuals from 482 families drawn from the Collaborative Study on the Genetics of Alcoholism (COGA), we performed a genome-wide association study (GWAS) on resting-state fast beta EEG power. To further characterize our genetic findings, we examined the functional and clinical/behavioral significance of GWAS variants. Ten correlated single-nucleotide polymorphisms (SNPs) (r>0.9) located in an intergenic region on chromosome 3q26 were associated with fast beta EEG power at P<5 × 10. The most significantly associated SNP, rs11720469 (β: -0.124; P<4.5 × 10), is also an expression quantitative trait locus for BCHE (butyrylcholinesterase), expressed in thalamus tissue. Four of the genome-wide SNPs were also associated with Diagnostic and Statistical Manual of Mental Disorders Alcohol Dependence in COGA AA families, and two (rs13093097, rs7428372) were replicated in an independent AA sample (Gelernter et al.). Analyses in the AA adolescent/young adult (offspring from COGA families) subsample indicated association of rs11720469 with heavy episodic drinking (frequency of consuming 5+ drinks within 24 h). Converging findings presented in this study provide support for the role of genetic variants within 3q26 in neural and behavioral disinhibition. These novel genetic findings highlight the importance of including AA populations in genetics research on SUDs and the utility of the endophenotype approach in enhancing our understanding of mechanisms underlying addiction susceptibility.
Genome-wide association results for fast beta electroencephalogram in the African-American ancestry function genome-wide association study. y Axis denotes the –log10(P-value) for association. x Axis is the physical position of the single-nucleotide polymorphisms across the genome. Note: Red line indicates the threshold of genome-wide significance (P<5 × 10−8), whereas the blue line indicates the threshold of P<5 × 10−5.
Association results for fast beta electroencephalogram on chromosome 3q26. y Axis denotes the –log10(P-value) for association. x Axis is the physical position on the chromosome (Mb). The most significantly associated single-nucleotide polymorphism (SNP; rs11720469) is shown in purple. The extent of linkage disequilibrium (LD; as measured by r2) between each SNP and the most significantly associated SNP is indicated by the color scale at the top left. Larger values of r2 indicate greater LD. Circles represent P-values from the African-American ancestry function genome-wide association study sample. LD is based on hg19 1000 Genomes from the African sample.
No entities extracted from this document yet.
No uploaded files.
In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Dimensional and transdiagnostic phenotypes in psychiatric genome-wide association studies. | Waszczuk MA et al. | — | 2023 | → |
| Genomic risk for post-traumatic stress disorder in families densely affected with alcohol use disorders. | Saenz de Viteri S et al. | — | 2023 | → |
| Predicting Alcohol-Related Memory Problems in Older Adults: A Machine Learning Study with Multi-Domain Features. | Kamarajan C et al. | — | 2023 | → |
| The collaborative study on the genetics of alcoholism: Brain function. | Meyers JL et al. | — | 2023 | → |
| A genome-wide association study of tinnitus reveals shared genetic links to neuropsychiatric disorders. | Bhatt IS et al. | — | 2022 | → |
| A scoping review of electroencephalographic (EEG) markers for tracking neurophysiological changes and predicting outcomes in substance use disorder treatment. | Bel-Bahar TS et al. | — | 2022 | → |
| Genome-wide association mapping of ethanol sensitivity in the Diversity Outbred mouse population. | Parker CC et al. | — | 2022 | → |
| Imaging Genetics in Epilepsy: Current Knowledge and New Perspectives. | Wang G et al. | — | 2022 | → |
| Long-Chain Acylcholines Link Butyrylcholinesterase to Regulation of Non-neuronal Cholinergic Signaling. | Kinchen JM et al. | — | 2022 | → |
| Targeting prefrontal cortex GABAergic microcircuits for the treatment of alcohol use disorder. | Fish KN et al. | — | 2022 | → |
| A genome-wide association study of interhemispheric theta EEG coherence: implications for neural connectivity and alcohol use behavior. | Meyers JL et al. | — | 2021 | → |
| Predicting risk for Alcohol Use Disorder using longitudinal data with multimodal biomarkers and family history: a machine learning study. | Kinreich S et al. | — | 2021 | → |
| Alcohol Sensitivity as an Endophenotype of Alcohol Use Disorder: Exploring Its Translational Utility between Rodents and Humans. | Parker CC et al. | — | 2020 | → |
| CR-19-0950: Event-related responses to alcohol-related stimuli in Mexican-American young adults: Relation to age, gender, comorbidity and "dark side" symptoms. | Ehlers CL et al. | — | 2019 | → |
| Genome-wide association studies of alcohol dependence, DSM-IV criterion count and individual criteria. | Lai D et al. | — | 2019 | → |
| Genome-wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward-related ventral striatum activity in African- and European-Americans. | Wetherill L et al. | — | 2019 | → |
| Human brain arousal in the resting state: a genome-wide association study. | Jawinski P et al. | — | 2019 | → |
| Conflict-related medial frontal theta as an endophenotype for alcohol use disorder. | Harper J et al. | — | 2018 | → |
| Effect of Gabapentin on Sleep and Event-Related Oscillations (EROs) in Rats Exposed to Chronic Intermittent Ethanol Vapor and Protracted Withdrawal. | Sanchez-Alavez M et al. | — | 2018 | → |
| Genome-wide association analysis links multiple psychiatric liability genes to oscillatory brain activity. | Smit DJA et al. | — | 2018 | → |
| Heritability of Sleep EEG Topography in Adolescence: Results from a Longitudinal Twin Study. | Markovic A et al. | — | 2018 | → |
| Polygenic Risk Scores in Clinical Psychology: Bridging Genomic Risk to Individual Differences. | Bogdan R et al. | — | 2018 | → |
| Genome-wide association analysis links multiple psychiatric liability genes to oscillatory brain activity | Smit DJ et al. | — | 2017 | — |
| Lack of associations of the opioid receptor mu 1 (OPRM1) A118G polymorphism (rs1799971) with alcohol dependence: review and meta-analysis of retrospective controlled studies. | Kong X et al. | — | 2017 | → |
| The Brain of Binge Drinkers at Rest: Alterations in Theta and Beta Oscillations in First-Year College Students with a Binge Drinking Pattern. | López-Caneda E et al. | — | 2017 | → |