QTLs Identified for P3 Amplitude in a Non-Clinical Sample: Importance of Neurodevelopmental and Neurotransmitter Genes

• Published in: Biological psychiatry (1969) 2008-05, Vol.63 (9), p.864-873
• Main Authors: Wright, Margaret J, Luciano, Michelle, Hansell, Narelle K, Montgomery, Grant W, Geffen, Gina M, Martin, Nicholas G
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Brain Mapping; Cerebral Cortex - physiopathology; Chromosome Mapping; Chromosomes, Human, Pair 6 - genetics; Chromosomes, Human, Pair 7 - genetics; Chromosomes, Human, Pair 9 - genetics; Cognition Disorders - genetics; Cognition Disorders - physiopathology; Developmental Disabilities - genetics; Developmental Disabilities - physiopathology; Diseases in Twins - genetics; Diseases in Twins - physiopathology; Event-Related Potentials, P300 - genetics; Event-Related Potentials, P300 - physiology; Female; Genetic Markers - genetics; Genetic Testing; Genotype; Humans; Linkage analysis; Lod Score; Male; Microsatellite Repeats; neurodevelopmental genes; Neuropsychological Tests; Neurotransmitter Agents - genetics; Neurotransmitter Agents - physiology; neurotransmitter genes; P3 amplitude; P3 latency; Phenotype; Polymorphism, Genetic - genetics; Psychiatry; Quantitative Trait Loci - genetics; Reaction Time - genetics; Reaction Time - physiology; Statistics as Topic; twins
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/j.biopsych.2007.09.002

Background The P3(00) event-related potential is an index of processing capacity (P3 amplitude) and stimulus evaluation (P3 latency) as well as a phenotypic marker of various forms of psychopathology where P3 abnormalities have been reported. Methods A genome-wide linkage scan of 400–761 autosomal markers, at an average spacing of 5–10 centimorgans (cM), was completed in 647 twins/siblings (306 families mostly comprising dizygotic twins), mean age 16.3, range 15.4–20.1 years, for whom P3 amplitude and latency data were available. Results Significant linkage for P3 amplitude was observed on chromosome 7q for the central recording site (logarithm-of-odds [LOD] = 3.88, p = .00002) and in the same region for both frontal (LOD = 2.19, p = .0015) and parietal (LOD = 1.67, p = .0053) sites, with multivariate analysis also identifying linkage in this region (LOD = 2.14, p = .0017). Suggestive linkage was also identified on 6p (LODmax = 2.49) and 12q (LODmax = 2.24), with other promising regions identified on 9q (LODmax = 2.14) and 10p (LODmax = 2.18). Less striking were the results for P3 latency; LOD > 1.5 were found on chromosomes 1q, 9q, 10q, 12q, and 19p. Conclusions This is a first step in the identification of genes for normal variation in the P3. Loci identified here for P3 amplitude suggest the possible importance of neurodevelopmental genes in addition to those influencing neurotransmitters, fitting with the evidence that P3 amplitude is sensitive to diverse types of brain abnormalities.