Heritability of Individual Psychotic Experiences Captured by Common Genetic Variants in a Community Sample of Adolescents

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 th...

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Main Authors:	Sieradzka, Dominika, Power, Robert A., Freeman, Daniel, Cardno, Alastair G., Dudbridge, Frank, Ronald, Angelica
Format:	Online
Language:	English
Published:	Springer US 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4561057/

id	pubmed-4561057
recordtype	oai_dc
spelling	pubmed-45610572015-09-11 Heritability of Individual Psychotic Experiences Captured by Common Genetic Variants in a Community Sample of Adolescents Sieradzka, Dominika Power, Robert A. Freeman, Daniel Cardno, Alastair G. Dudbridge, Frank Ronald, Angelica Original Research 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. Springer US 2015-06-07 2015 /pmc/articles/PMC4561057/ /pubmed/26049723 http://dx.doi.org/10.1007/s10519-015-9727-5 Text en © The Author(s) 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Sieradzka, Dominika Power, Robert A. Freeman, Daniel Cardno, Alastair G. Dudbridge, Frank Ronald, Angelica
spellingShingle	Sieradzka, Dominika Power, Robert A. Freeman, Daniel Cardno, Alastair G. Dudbridge, Frank Ronald, Angelica Heritability of Individual Psychotic Experiences Captured by Common Genetic Variants in a Community Sample of Adolescents
author_facet	Sieradzka, Dominika Power, Robert A. Freeman, Daniel Cardno, Alastair G. Dudbridge, Frank Ronald, Angelica
author_sort	Sieradzka, Dominika
title	Heritability of Individual Psychotic Experiences Captured by Common Genetic Variants in a Community Sample of Adolescents
title_short	Heritability of Individual Psychotic Experiences Captured by Common Genetic Variants in a Community Sample of Adolescents
title_full	Heritability of Individual Psychotic Experiences Captured by Common Genetic Variants in a Community Sample of Adolescents
title_fullStr	Heritability of Individual Psychotic Experiences Captured by Common Genetic Variants in a Community Sample of Adolescents
title_full_unstemmed	Heritability of Individual Psychotic Experiences Captured by Common Genetic Variants in a Community Sample of Adolescents
title_sort	heritability of individual psychotic experiences captured by common genetic variants in a community sample of adolescents
description	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.
publisher	Springer US
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4561057/
_version_	1613473103065645056

Heritability of Individual Psychotic Experiences Captured by Common Genetic Variants in a Community Sample of Adolescents

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