Common genetic origins for EEG, alcoholism and anxiety: the role of CRH-BP.
- Authors
- Enoch, Mary-Anne; Shen, Pei-Hong; Ducci, Francesca; Yuan, Qiaoping; Liu, Jixia; White, Kenneth V; Albaugh, Bernard; Hodgkinson, Colin A; Goldman, David
- Year
- 2008
- Journal
- PloS one
- PMID
- 18974851
- DOI
- 10.1371/journal.pone.0003620
- PMCID
- PMC2575401
The resting EEG is a dynamic index of cortical activation, cognitive function and consciousness and is therefore an intermediate phenotype for many behaviors in which arousal is implicated such as anxiety and alcoholism. We performed a dense whole genome linkage scan using 3878 unlinked SNPs in a large pedigree derived from a population isolate sample of 328 Plains American Indians. Alpha (8-13 Hz), theta (4-8 Hz) and beta (13-30 Hz) EEG power was heritable (0.58-0.27) and stable over a 2 year period (r = 0.82-0.53). Genetic correlations between frequency bands were high (0.75). Linkage peaks for EEG power in all three frequency bands converged on chromosome 5q13-14 with genome-wide significant LOD scores of 3.5 (empirical p<0.0001) for alpha and beta power. A logical candidate gene, corticotropin releasing hormone-binding protein (CRH-BP), was located at the apex of these convergent linkage peaks. CRH-BP was significantly associated with alpha power in the Plains Indians and also in a replication sample of 188 Caucasians. Moreover, the same SNPs and haplotypes, located within the CRH-BP haplotype block, were also associated with anxiety disorders in the Plains Indians and alcohol use disorders in the Caucasians. CRH-BP modulates CRH which influences cortical and hippocampal EEG activity and is the primary mediator of the neuroendocrine stress response. Our results suggest a likely role for CRH-BP in stress-related alcoholism and highlight the use of the resting EEG as an intermediate phenotype for arousal-related behaviors such as anxiety and addiction.
Chromosome 5q13-14: Convergence of Linkage Peaks for Alpha (8–13 Hz) and Beta (13–30 Hz) EEG power.Only linkage peaks with LOD scores>3.0 are shown here. CRH-BP = corticotropin releasing hormone-binding protein gene. O1 = occipital electrode; P3, PZ, P4 = parietal electrodes.
CRH-BP Gene Map and Haplotype Block Structure in Plains Indians and U.S. Caucasians. CRH-BP: corticotropin releasing hormone-binding protein gene. 2A: The 7 CRH-BP exons are indicated by rectangles. An alternative isoform (CRH-BP alt) expressed in the brain has exon 7 spliced out. The positions of the genotyped SNPs are indicated and the 4 SNPs with significant associations with EEG power are highlighted. The haplotype block structures of the three HapMap populations: CEU (Caucasian); YRI (African) and ASN (Chinese/Japanese) are provided. Conservation across 17 vertebrate species, from zebrafish to humans is indicated (www.genome.ucsc.edu). 2B, 2C: haplotype block structure across the two populations. The numbers are D′ values (linkage disequilibrium between SNP pairs).
CRH-BP Peptide Sequence Conservation.The sequence of the human alternate isoform (H_Alt) is shown in the top line: the terminal 52 amino acids are deleted and replaced by 18 novel amino acids. Line 2 downward through line 8 shows strong sequence conservation between: human/chimp/macaque/dog/cow/rat/mouse/chicken respectively.
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| Corticotropin-releasing factor receptor signaling and modulation: implications for stress response and resilience. | Vasconcelos M et al. | — | 2020 | → |
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| Addiction and stress: An allostatic view. | Koob GF et al. | — | 2019 | → |
| Generating Brain Waves, the Power of Astrocytes. | Buskila Y et al. | — | 2019 | → |
| Association between stress pathway gene (CRHR1⧹CRHBP) polymorphisms and heroin dependence. | Su H et al. | — | 2018 | → |
| Evaluation of Alcohol Preference and Drinking in msP Rats Bearing a <i>Crhr1</i> Promoter Polymorphism. | Logrip ML et al. | — | 2018 | → |
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| HPA-axis genes as potential risk variants for neurocognitive decline in trauma-exposed, HIV-positive females. | Jacobs S et al. | — | 2018 | → |
| Interaction Between Stress and Addiction: Contributions From Latin-American Neuroscience. | Torres-Berrio A et al. | — | 2018 | → |
| Temporal stability of posterior EEG alpha over twelve years. | Tenke CE et al. | — | 2018 | → |
| The corticotropin releasing factor binding protein: A strange case of Dr. Jekyll and Mr. Hyde in the stress system? | Haass-Koffler CL | — | 2018 | → |
| Cell Type-Specific Expression of Corticotropin-Releasing Hormone-Binding Protein in GABAergic Interneurons in the Prefrontal Cortex. | Ketchesin KD et al. | — | 2017 | → |
| Corticotropin-releasing hormone-binding protein and stress: from invertebrates to humans. | Ketchesin KD et al. | — | 2017 | → |
| Quantitative EEG during normal aging: association with the Alzheimer's disease genetic risk variant in PICALM gene. | Ponomareva NV et al. | — | 2017 | → |
| Review: Genetic and environmental risk factors for alcohol use disorders in American Indians and Alaskan Natives. | Enoch MA et al. | — | 2017 | → |
| Whole genome sequence association and ancestry-informed polygenic profile of EEG alpha in a Native American population. | Peng Q et al. | — | 2017 | → |
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| Endophenotypes for Alcohol Use Disorder: An Update on the Field. | Salvatore JE et al. | — | 2015 | → |
| Genetic variants in hypothalamic-pituitary-adrenal axis genes and breast cancer risk in Caucasians and African Americans. | Nan H et al. | — | 2015 | → |
| Multivariate genetic determinants of EEG oscillations in schizophrenia and psychotic bipolar disorder from the BSNIP study. | Narayanan B et al. | — | 2015 | → |
| Preclinical evidence implicating corticotropin-releasing factor signaling in ethanol consumption and neuroadaptation. | Phillips TJ et al. | — | 2015 | → |
| Relative brain signature: a population-based feature extraction procedure to identify functional biomarkers in the brain of alcoholics. | Karamzadeh N et al. | — | 2015 | → |
| Association of innate immune single-nucleotide polymorphisms with the electroencephalogram during desflurane general anaesthesia. | Mulholland CV et al. | — | 2014 | → |
| Corticotropin releasing factor: a key role in the neurobiology of addiction. | Zorrilla EP et al. | — | 2014 | → |
| Drug addiction and stress-response genetic variability: association study in African Americans. | Levran O et al. | — | 2014 | → |
| Genotyping and development of single-nucleotide polymorphism (SNP) markers associated with blast resistance genes in rice using GoldenGate assay | Thakur S et al. | — | 2014 | — |
| Heritability and molecular-genetic basis of resting EEG activity: a genome-wide association study. | Malone SM et al. | — | 2014 | → |
| Interpreting EEG alpha activity. | Bazanova OM et al. | — | 2014 | → |
| Personalized Medicine in ADHD and Depression: Use of Pharmaco-EEG. | Arns M et al. | — | 2014 | → |
| Unique genetic loci identified for emotional behavior in control and chronic stress conditions. | Carhuatanta KA et al. | — | 2014 | → |
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| Behavioral, biological, and chemical perspectives on targeting CRF(1) receptor antagonists to treat alcoholism. | Zorrilla EP et al. | — | 2013 | → |
| Corticotropin-releasing hormone system polymorphisms are associated with children's cortisol reactivity. | Sheikh HI et al. | — | 2013 | → |
| Evidence for a genetic component for substance dependence in Native Americans. | Ehlers CL et al. | — | 2013 | → |
| Peak individual alpha frequency qualifies as a stable neurophysiological trait marker in healthy younger and older adults. | Grandy TH et al. | — | 2013 | → |
| Role of a genetic polymorphism in the corticotropin-releasing factor receptor 1 gene in alcohol drinking and seeking behaviors of marchigian sardinian alcohol-preferring rats. | Ayanwuyi LO et al. | — | 2013 | → |
| A prospective study of stress and alcohol craving in heavy drinkers. | Tartter MA et al. | — | 2012 | → |
| Relevance of both type-1 and type-2 corticotropin releasing factor receptors in stress-induced relapse to cocaine seeking behaviour. | Gysling K | — | 2012 | → |
| The relationship of appetitive, reproductive and posterior pituitary hormones to alcoholism and craving in humans. | Kenna GA et al. | — | 2012 | → |
| Two HPA axis genes, CRHBP and FKBP5, interact with childhood trauma to increase the risk for suicidal behavior. | Roy A et al. | — | 2012 | → |
| Genetic association study of GABRA2 single nucleotide polymorphisms and electroencephalography in alcohol dependence. | Lydall GJ et al. | — | 2011 | → |
| Molecular signaling and translational significance of the corticotropin releasing factor system. | Ronan PJ et al. | — | 2011 | → |
| Neurotransmitter and neuromodulator genes associated with a history of depressive symptoms in individuals with alcohol dependence. | Kertes DA et al. | — | 2011 | → |
| Role of corticotropin-releasing factor in drug addiction: potential for pharmacological intervention. | Logrip ML et al. | — | 2011 | → |
| Stress-induced and cue-induced craving for alcohol in heavy drinkers: Preliminary evidence of genetic moderation by the OPRM1 and CRH-BP genes. | Ray LA | — | 2011 | → |
| Binge drinking effects on EEG in young adult humans. | Courtney KE et al. | — | 2010 | → |
| EEG alpha phenotypes: linkage analyses and relation to alcohol dependence in an American Indian community study. | Ehlers CL et al. | — | 2010 | → |
| Genome-wide association identifies candidate genes that influence the human electroencephalogram. | Hodgkinson CA et al. | — | 2010 | → |
| Single-nucleotide polymorphisms in corticotropin releasing hormone receptor 1 gene (CRHR1) are associated with quantitative trait of event-related potential and alcohol dependence. | Chen AC et al. | — | 2010 | → |
| The CRF system, stress, depression and anxiety-insights from human genetic studies. | Binder EB et al. | — | 2010 | → |
| The functional Val158Met polymorphism of COMT predicts interindividual differences in brain alpha oscillations in young men. | Bodenmann S et al. | — | 2009 | → |