title: Heritability of Individual Psychotic Experiences Captured by Common Genetic Variants in a Community Sample of Adolescents.
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.
authors.affiliation: Centre for Brain and Cognitive Development, Birkbeck, University of London, 32 Torrington Square, London, WC1E 7HX, UK, dsiera01@mail.bbk.ac.uk.
authors.forename: Dominika
authors.initials: D
authors.lastname: Sieradzka
authors.forename: Robert A
authors.initials: RA
authors.lastname: Power
authors.forename: Daniel
authors.initials: D
authors.lastname: Freeman
authors.forename: Alastair G
authors.initials: AG
authors.lastname: Cardno
authors.forename: Frank
authors.initials: F
authors.lastname: Dudbridge
authors.forename: Angelica
authors.initials: A
authors.lastname: Ronald
mesh_terms: D000293:Adolescent; D004200:Diseases in Twins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000235:genetics*; D011795:Surveys and Questionnaires; D014427:Twins / Q000235:genetics