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

Mistry, Sumit, Harrison, Judith, Smith, Daniel J, Escott-Price, Valentina and Zammit, Stanley 2018. The use of polygenic risk scores to identify phenotypes associated with genetic risk of schizophrenia: systematic review. Schizophrenia Research 197 , pp. 2-8. 10.1016/j.schres.2017.10.037
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Abstract

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 less than 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: Article
Date Type: Publication
Status: Published
Schools: Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > R Medicine (General)
Publisher: Elsevier
ISSN: 0920-9964
Last Modified: 29 Sep 2018 07:32
URI: http://orca-mwe.cf.ac.uk/id/eprint/106084

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