Elsevier

Biological Psychiatry

Volume 63, Issue 9, 1 May 2008, Pages 864-873
Biological Psychiatry

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

https://doi.org/10.1016/j.biopsych.2007.09.002Get rights and content

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.

Section snippets

Participants

The sample included 306 families consisting of 227 dizygotic twin pairs (183: 0 singleton siblings; 44: 1–3 singleton siblings), 33 monozygotic pairs (8: 0 siblings; 25: 1–2 siblings), 9 sib-pairs, and 37 single twins/non-paired singletons, for which both the P3 phenotypes and linkage scan were available. Mean age at time of P3 data collection was 16.3 (± .49), range 15.4–20.1 years. Families were part of a larger sample participating in an ongoing study of cognition (49) and for which P3 data

Results

Genome scan results for P3 amplitude and P3 latency are shown in Figure 2, Figure 3, respectively (displayed as p values so that the first multivariate test [Multiv-I] can be directly compared with the univariate tests). Univariate analyses for P3 amplitude yielded significant linkage on chromosome 7q (peak marker D7S2204) for the central measure (LOD = 3.88, p = .000024), with a trait specific QTL heritability of 22%. In the same region a linkage peak, albeit at a more modest level of

Discussion

Here we describe the first genomewide screen for P3 amplitude and latency in a non-clinical sample of sib-pairs. We identified a novel locus for P3 amplitude on chromosome 7q. There was also suggestive evidence for P3 amplitude loci on 6p and 12q as well as promising loci identified on 9q and 10p. In contrast, evidence for linkage for P3 latency was less compelling, with no peaks reaching either the significant or suggestive level; so these must await independent replication.

A single region on

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