Common genetic origins for EEG, alcoholism and anxiety: the role of CRH-BP

PLoS One. 2008;3(10):e3620. doi: 10.1371/journal.pone.0003620. Epub 2008 Oct 31.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Alcoholism / ethnology
  • Alcoholism / genetics*
  • Anxiety / ethnology
  • Anxiety / genetics*
  • Brain / physiology
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Chromosomes, Human, Pair 5
  • Electroencephalography*
  • Environment
  • Genome-Wide Association Study
  • Humans
  • Linkage Disequilibrium
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Quantitative Trait, Heritable
  • Rest / physiology

Substances

  • Carrier Proteins
  • corticotropin releasing factor-binding protein