The use of polygenic risk scores to identify phenotypes associated with genetic risk of bipolar disorder and depression: a 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 bipolar disorder and depression: a systematic review. Journal of Affective Disorders, 234, pp. 148-155. (doi:10.1016/j.jad.2018.02.005) (PMID:29529547)

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 bipolar disorder and depression: a systematic review. Journal of Affective Disorders, 234, pp. 148-155. (doi:10.1016/j.jad.2018.02.005) (PMID:29529547)

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Abstract

Background: Identifying the phenotypic manifestations of increased genetic liability for depression (MDD) and bipolar disorder (BD) can enhance understanding of their aetiology. The polygenic risk score (PRS) derived using data from genome-wide-association-studies can be used to explore how genetic risk is manifest in different samples. Aims: In this systematic review, we review studies that examine associations between the MDD and BD polygenic risk scores and phenotypic outcomes. Methods: Following PRISMA guidelines, we searched EMBASE, Medline and PsycINFO (from August 2009 – 14th March 2016) and references of included studies. Study inclusion was based on predetermined criteria and data were extracted independently and in duplicate. Results: Twenty-five studies were included. Overall, both polygenic risk scores were associated with other psychiatric disorders (not the discovery sample disorder) such as depression, schizophrenia and bipolar disorder, greater symptom severity of depression, membership of a creative profession and greater educational attainment. Both depression and bipolar polygenic risk scores explained small amounts of variance in most phenotypes (< 2%). Limitations: Many studies did not report standardised effect sizes. This prevented us from conducting a meta-analysis. Conclusions: Polygenic risk scores for BD and MDD are associated with a range of phenotypes and outcomes. However, they only explain a small amount of the variation in these phenotypes. Larger discovery and adequately powered target samples are required to increase power of the PRS approach. This could elucidate how genetic risk for bipolar disorder and depression is manifest and contribute meaningfully to stratified medicine.

Item Type:Articles
Additional Information:SM is funded by Mental Health Research UK. DJS is a Lister Institute Prize Fellow (2016–2021). JRH is funded by the Wellcome Trust GW4 Clinical Academic Training Fellowship. This study was supported by the NIHR Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol.
Status:Published
Refereed:Yes
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:Journal of Affective Disorders
Publisher:Elsevier
ISSN:0165-0327
ISSN (Online):1573-2517
Published Online:15 February 2018
Copyright Holders:Copyright © 2018 Elsevier B.V.
First Published:First published in Journal of Affective Disorders 234: 148-155
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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