The use of polygenic risk scores to identify phenotypes associated with genetic risk of schizophrenia: systematic review

Mistry, S., Harrison, J. R., Smith, D. J. , Escott-Price, V. and Zammit, S. (2018) The use of polygenic risk scores to identify phenotypes associated with genetic risk of schizophrenia: systematic review. Schizophrenia Research, 197, pp. 2-8. (doi:10.1016/j.schres.2017.10.037) (PMID:29129507)

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Studying the phenotypic manifestations of increased genetic liability for schizophrenia can increase our understanding of this disorder. Specifically, information from alleles identified in genome-wide association studies can be collapsed into a polygenic risk score (PRS) to explore how genetic risk is manifest within different samples. In this systematic review, we provide a comprehensive assessment of studies examining associations between schizophrenia PRS (SZ-PRS) and several phenotypic measures. We searched EMBASE, Medline and PsycINFO (from August 2009–14th March 2016) plus references of included studies, following PRISMA guidelines. Study inclusion was based on predetermined criteria and data were extracted independently and in duplicate. Overall, SZ-PRS was associated with increased risk for psychiatric disorders such as depression and bipolar disorder, lower performance IQ and negative symptoms. SZ-PRS explained up to 6% of genetic variation in psychiatric phenotypes, compared to < 0.7% in measures of cognition. Future gains from using the PRS approach may be greater if used for examining phenotypes that are more closely related to biological substrates, for scores based on gene-pathways, and where PRSs are used to stratify individuals for study of treatment response. As it was difficult to interpret findings across studies due to insufficient information provided by many studies, we propose a framework to guide robust reporting of PRS associations in the future.

Item Type:Articles
Keywords:Polygenic risk score, schizophrenia, genetic, phenotypes.
Glasgow Author(s) Enlighten ID:Smith, Professor Daniel
Authors: Mistry, S., Harrison, J. R., Smith, D. J., Escott-Price, V., and Zammit, S.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Mental Health and Wellbeing
Journal Name:Schizophrenia Research
ISSN (Online):1573-2509
Published Online:10 November 2017
Copyright Holders:Copyright © 2017 Crown Copyright
First Published:First published in Schizophrenia Research 197: 2-8
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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