Schizophrenia polygenic risk and experiences of childhood adversity: a systematic review and meta-analysis

Woolway, Grace, Smart, Sophie ORCID: https://orcid.org/0000-0002-6709-5425, Lynham, Amy ORCID: https://orcid.org/0000-0002-3189-6888, Lloyd, Jennifer, Owen, Michael ORCID: https://orcid.org/0000-0003-4798-0862, Jones, Ian ORCID: https://orcid.org/0000-0001-5821-5889, Walters, James ORCID: https://orcid.org/0000-0002-6980-4053 and Legge, Sophie 2022. Schizophrenia polygenic risk and experiences of childhood adversity: a systematic review and meta-analysis. Schizophrenia Bulletin 48 (5) , pp. 967-980. 10.1093/schbul/sbac049

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Abstract

Background and Hypothesis Schizophrenia has been robustly associated with multiple genetic and environmental risk factors. Childhood adversity is one of the most widely replicated environmental risk factors for schizophrenia, but it is unclear if schizophrenia genetic risk alleles contribute to this association. Study Design In this systematic review and meta-analysis, we assessed the evidence for gene-environment correlation (genes influence likelihood of environmental exposure) between schizophrenia polygenic risk score (PRS) and reported childhood adversity. We also assessed the evidence for a gene-environment interaction (genes influence sensitivity to environmental exposure) in relation to the outcome of schizophrenia and/or psychosis. This study was registered on PROSPERO (CRD42020182812). Following PRISMA guidelines, a search for relevant literature was conducted using Cochrane, MEDLINE, PsycINFO, Web of Science, and Scopus databases until February 2022. All studies that examined the association between schizophrenia PRS and childhood adversity were included. Study Results Seventeen of 650 identified studies met the inclusion criteria and were assessed against the Newcastle-Ottawa Scale for quality. The meta-analysis found evidence for gene-environment correlation between schizophrenia PRS and childhood adversity (r = .02; 95% CI = 0.01, 0.03; P = .001), but the effect was small and therefore likely to explain only a small proportion of the association between childhood adversity and psychosis. The 4 studies that investigated a gene-environment interaction between schizophrenia PRS and childhood adversity in increasing risk of psychosis reported inconsistent results. Conclusions These findings suggest that a gene-environment correlation could explain a small proportion of the relationship between reported childhood adversity and psychosis.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Additional Information:	This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/)
Publisher:	Oxford University Press
ISSN:	0586-7614
Funders:	MRC
Date of First Compliant Deposit:	11 May 2022
Date of Acceptance:	3 May 2022
Last Modified:	11 Oct 2023 18:52
URI:	https://orca.cardiff.ac.uk/id/eprint/149681

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