Abstract
Occurrence of psychotic experiences is common amongst adolescents in the general population. Twin studies suggest that a third to a half of variance in adolescent psychotic experiences is explained by genetic influences. Here we test the extent to which common genetic variants account for some of the twin-based heritability. Psychotic experiences were assessed with the Specific Psychotic Experiences Questionnaire in a community sample of 2152 16-year-olds. Self-reported measures of Paranoia, Hallucinations, Cognitive Disorganization, Grandiosity, Anhedonia, and Parent-rated Negative Symptoms were obtained. Estimates of SNP heritability were derived and compared to the twin heritability estimates from the same sample. Three approaches to genome-wide restricted maximum likelihood (GREML) analyses were compared: (1) standard GREML performed on full genome-wide data; (2) GREML stratified by minor allele frequency (MAF); and (3) GREML performed on pruned data. The standard GREML revealed a significant SNP heritability of 20 % for Anhedonia (SE = 0.12; p < 0.046) and an estimate of 19 % for Cognitive Disorganization, which was close to significant (SE = 0.13; p < 0.059). Grandiosity and Paranoia showed modest SNP heritability estimates (17 %; SE = 0.13 and 14 %; SE = 0.13, respectively, both n.s.), and zero estimates were found for Hallucinations and Negative Symptoms. The estimates for Anhedonia, Cognitive Disorganization and Grandiosity accounted for approximately half the previously reported twin heritability. SNP heritability estimates from the MAF-stratified approach were mostly consistent with the standard estimates and offered additional information about the distribution of heritability across the MAF range of the SNPs. In contrast, the estimates derived from the pruned data were for the most part not consistent with the other two approaches. It is likely that the difference seen in the pruned estimates was driven by the loss of tagged causal variants, an issue fundamental to this approach. The current results suggest that common genetic variants play a role in the etiology of some adolescent psychotic experiences, however further research on larger samples is desired and the use of MAF-stratified approach recommended.
Highlights
Occurrence of psychotic experiences is common amongst adolescents in the general population
Three approaches to genome-wide restricted maximum likelihood (GREML) analyses were compared: (1) standard GREML performed on full genome-wide data; (2) GREML stratified by minor allele frequency (MAF); and (3) GREML performed on Edited by Michael Lyons
Point estimates for Hallucinations and Parent-rated Negative Symptoms were low, which was consistent across all three approaches. These results suggest that detection of common single nucleotide polymorphisms (SNPs) associated with hallucinations and parent-rated negative symptoms may prove to be more difficult than identifying common SNPs associated with adolescent anhedonia, cognitive disorganization, grandiosity or paranoia because the former appear to have less net variance explained by common SNPs than the latter
Summary
Occurrence of psychotic experiences is common amongst adolescents in the general population. The estimates for Anhedonia, Cognitive Disorganization and Grandiosity accounted for approximately half the previously reported twin heritability. The current results suggest that common genetic variants play a role in the etiology of some adolescent psychotic experiences, further research on larger samples is desired and the use of MAF-stratified approach recommended. ‘Psychotic experiences’ is an umbrella term for a range of phenomena including paranoia, hallucinations, lack of motivation or inability to experience pleasure These experiences are common but vary in severity of expression across the population (van Os et al 2009; Ronald et al 2014). Ronald et al (2014) have identified a sixdimensional solution of paranoia, hallucinations, cognitive disorganization, grandiosity, anhedonia, and negative symptoms, from the same sample as was employed in the current study The number of reported dimensions and their content vary depending on the measure of psychotic experiences used, it is usually three or more (Cyhlarova and Claridge 2005; Fonseca-Pedrero et al 2009; Ericson et al 2011; Wigman et al 2011; Ronald et al 2014). Ronald et al (2014) have identified a sixdimensional solution of paranoia, hallucinations, cognitive disorganization, grandiosity, anhedonia, and negative symptoms, from the same sample as was employed in the current study
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