Heritability and molecular‐genetic basis of resting EEG activity: A genome‐wide association study

Abstract

Several EEG parameters are potential endophenotypes for different psychiatric disorders. The present study consists of a comprehensive behavioral- and molecular-genetic analysis of such parameters in a large community sample (N = 4,026) of adolescent twins and their parents, genotyped for 527,829 single nucleotide polymorphisms (SNPs). Biometric heritability estimates ranged from .49 to .85, with a median of .78. The additive effect of all SNPs (SNP heritability) varied across electrodes. Although individual SNPs were not significantly associated with EEG parameters, several genes were associated with delta power. We also obtained an association between the GABRA2 gene and beta power (p < .014), consistent with findings reported by others, although this did not survive Bonferroni correction. If EEG parameters conform to a largely polygenic model of inheritance, larger sample sizes will be required to detect individual variants reliably.

Electrophysiological Endophenotypes for Schizophrenia

“…Lastly, while there is ample evidence that P300 amplitude is heritable, lack of replication remains a problem for discovering specific genetic contributions to this endophenotype. 60,172,181,193 …”

The Power of Theory, Research Design, and Transdisciplinary Integration in Moving Psychopathology Forward

“…Endophenotypes, such as the P3, are typically promoted for their supposed assistance in genetic association studies, but they have yet to demonstrate their promise for gene finding (Malone, Vaidyanathan, et al, 2014; G. A. Miller & Rockstroh, 2013; Vrieze, Malone, Pankratz, et al, 2014; Vrieze, Malone, Vaidyanathan, et al, 2014).…”

“…In fact, we recently completed a comprehensive evaluation of endophenotypes using psychophysiological and molecular genetic data from paradigms examining P3, the startle blink response, antisaccade eye tracking performance, skin conductance orienting and habituation, and resting electronencephalogram (EEG) frequency band power. Employing a sample of approximately 5000 people, we subjected these putative endophenotypes to a risky test (Iacono, Malone, Vaidyanathan, & Vrieze, 2014; Iacono, Vaidyanathan, Vrieze, & Malone, 2014; Malone, Burwell, et al, 2014; Malone, Vaidyanathan, et al, 2014; Vaidyanathan, Isen, et al, 2014; Vaidyanathan, Malone, et al, 2014; Vaidyanathan, Malone, Miller, McGue, & Iacono, 2014; Vrieze, Malone, Pankratz, et al, 2014; Vrieze, Malone, Vaidyanathan, et al, 2014). While most of the indices in our sample were heritable in conventional biometric twin models, in molecular genetic tests, whether we examined GWAS common SNPs, rare variants via exome-sequencing, or used whole genome sequencing, we found little credible evidence that any of the molecular variants was associated with any of the indices.…”

Cracking the brain’s genetic code

“…See companion article on page 15462. cortical gray matter thickness (8), the size of subcortical structures (9), the hemodynamic response in functional MRI (10), and even the pattern of brain synchrony seen with EEG (11). The brain's anatomical network, the so-called structural "connectome," is under remarkably tight genetic control: Powerful algorithms are now screening these networks for markers in the genome that affect them (12).…”