Common Genetic Origins for EEG, Alcoholism and Anxiety: The Role of CRH-BP

• Published in: PloS one Vol. 3; no. 10; p. e3620
• Main Authors: Enoch, Mary-Anne, Shen, Pei-Hong, Ducci, Francesca, Yuan, Qiaoping, Liu, Jixia, White, Kenneth V., Albaugh, Bernard, Hodgkinson, Colin A., Goldman, David
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.10.2008; Public Library of Science (PLoS)
• Subjects: Addictions; Alcoholism; Alcoholism - ethnology; Alcoholism - genetics; Alcohols; Anxiety; Anxiety - ethnology; Anxiety - genetics; Arousal; Brain - physiology; Carrier Proteins - genetics; Carrier Proteins - physiology; Chromosome 5; Chromosomes, Human, Pair 5; Cognitive ability; Consciousness; Convergence; Cortex; Corticotropin; Corticotropin-releasing hormone; Disorders; Drug abuse; EEG; Electroencephalography; Environment; Frequencies; Genetic aspects; Genetics and Genomics/Complex Traits; Genetics and Genomics/Genetics of Disease; Genome-Wide Association Study; Genomes; Genomics; Haplotypes; Hippocampus; Humans; Linkage Disequilibrium; Native Americans; Neurohormones; Neurological Disorders/Neurogenetics; Neurological Disorders/Neuropsychiatric Disorders; Neuroscience/Behavioral Neuroscience; Pedigree; Phenotype; Polymorphism, Single Nucleotide; Protein binding; Quantitative Trait, Heritable; Rest - physiology; Single-nucleotide polymorphism; Spectrum analysis; Studies; United States > US; Maryland
• DOI: 10.1371/journal.pone.0003620
• ISSN: 1932-6203

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.