Heritability and molecular-genetic basis of the P3 event-related brain potential: a genome-wide association study.
P3 amplitude is a candidate endophenotype for disinhibitory psychopathology, psychosis, and other disorders. The present study is a comprehensive analysis of the behavioral- and molecular-genetic basis of P3 amplitude and a P3 genetic factor score in a large community sample (N = 4,211) of adolescent twins and their parents, genotyped for 527,829 single nucleotide polymorphisms (SNPs). Biometric models indicated that as much as 65% of the variance in each measure was due to additive genes. All SNPs in aggregate accounted for approximately 40% to 50% of the heritable variance. However, analyses of individual SNPs did not yield any significant associations. Analyses of individual genes did not confirm previous associations between P3 amplitude and candidate genes but did yield a novel association with myelin expression factor 2 (MYEF2). Main effects of individual variants may be too small to be detected by GWAS without larger samples.
Department of Psychology, University of Minnesota, Minneapolis, Minnesota, USA.
Stephen M
SM
Malone
Uma
U
Vaidyanathan
Saonli
S
Basu
Michael B
MB
Miller
Matt
M
McGue
William G
WG
Iacono
D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000502:physiology*; D004569:Electroencephalography; D058068:Endophenotypes; D018913:Event-Related Potentials, P300 / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D020641:Polymorphism, Single Nucleotide; D014427:Twins / Q000235:genetics*; D055815:Young Adult
Endophenotype; GCTA; Gene-based tests; Genome-wide association study; Heritability; Molecular genetics; P300